[{"pathScore":"-2.736","depth":0,"reaction":{"label":">>0","id":0,"pathId":6},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":4,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":6}]},{"depth":4,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":6}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":6}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":6}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":6}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":6}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":6}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":6}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-4.409","depth":0,"reaction":{"label":">>0","id":0,"pathId":697},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":697}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":697}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":697}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":697}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":697}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":697}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":697}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":697}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":697}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-4.788","depth":0,"reaction":{"label":">>0","id":0,"pathId":39},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":39}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":39}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":39}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":39}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":39}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":39}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":39}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":39}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":39}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":39}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-4.799","depth":0,"reaction":{"label":">>0","id":0,"pathId":4},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":5,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":4}]},{"depth":5,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":4}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":4}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":4}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":4}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":4}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":4}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":4}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":4}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":4}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-4.825","depth":0,"reaction":{"label":">>0","id":0,"pathId":22},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":22}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":22}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":22}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":22}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":22}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":22}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":22}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":22}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":22}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":22}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-4.907","depth":0,"reaction":{"label":">>0","id":0,"pathId":7},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":5,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":7}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":7}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":7}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":4,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":7}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":7}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":7}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":7}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":7}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":7}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":7}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-5.122","depth":0,"reaction":{"label":">>0","id":0,"pathId":2068},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.002469778060913086,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9975302219390869,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.002480626106262207,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9975193738937378,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(C(C)C)C(C)C\",\"distance\":0.0029109716415405273,\"rxn_id\":\"ord-fbc6602e838844ea8049e8f1cc4695df\",\"index\":724691,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"procedure_details\":\"Diisopropylethylamine (0.09 ml, 0.5 mmol) was added in one portion to a stirred solution of 4-amino-N-(2-morpholin-4-yl-ethyl)-benzenesulfonamide (0.1 g, 0.35 mmol) in THF (3 ml) at room temperature. To this mixture was added acryloyl chloride (0.03 ml, 0.38 mmol) in one portion and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After this time, the mixture was concentrated under vacuum and the resulting residue purified by Prep HPLC to give the title compound (6 mg, 5% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9970890283584595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_str\":\"C(N(C(C)C)CC)(C)C.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[N:23]1([CH2:22][CH2:21][NH:20][S:17]([C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:16][CH:15]=2)(=[O:19])=[O:18])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1\",\"yield_000\":5.1},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0030384063720703125,\"rxn_id\":\"ord-3e531f95b682495d934d2f5fe24064c6\",\"index\":208714,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"procedure_details\":\"4-(4-Amino-benzenesulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.25 g, 0.67 mmol) was dissolved in THF (10 ml). To this was added diisopropylethylamine (0.33 ml, 1.9 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.06 ml, 0.74 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material was purified by column chromatography (elution: 20% heptane, 80% ethyl acetate) to give the title compound (57 mg, 20% yield) as a white powder.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9969615936279297,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:36](=[O:39])[CH:37]=[CH2:38])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":19.8},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.003479301929473877,\"rxn_id\":\"ord-2a9510bf8eea48eb89d49af6327453f4\",\"index\":594742,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"procedure_details\":\"4-(4-Amino-2-trifluoromethyl-benzensulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.44 g, 0.11 mmol) was dissolved in THF (15 ml). To this solution was added diisopropylethylamine (0.52 ml, 0.33 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.09 ml, 0.11 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material, was purified by preparative HPLC to give the title compound (70 mg, 14% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9965206980705261,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=2[C:27]([F:30])([F:29])[F:28])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:40](=[O:43])[CH:41]=[CH2:42])=[CH:22][C:21]=2[C:27]([F:30])([F:28])[F:29])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":127.9}]","literatureScore":1,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":2068}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":2068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2068}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":2068}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":2068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":2068}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.62,"id":37,"pathId":2068}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.62,"id":7,"pathId":2068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2068}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:22]1[cH:23][c:24]([c:25]([cH:27][c:21]1[NH:20][c:19]2[c:18]3[cH:33][c:34]([c:15]([cH:16][c:17]3[n+:31]([cH:30][n:29]2)[O-:32])[O:14][CH2:13][CH2:12][CH2:11][N:10]4[CH2:5][CH2:6][O:7][CH2:8][CH2:9]4)[NH2:35])[Cl:26])[F:28]>C1CCOC1.C(N(CC)C(C)C)(C)C>[CH2:4]=[CH:3][C:1](=[O:2])[NH:35][c:34]1[cH:33][c:18]2[c:17]([cH:16][c:15]1[O:14][CH2:13][CH2:12][CH2:11][N:10]3[CH2:5][CH2:6][O:7][CH2:8][CH2:9]3)[n+:31]([cH:30][n:29][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:25]([cH:27]4)[Cl:26])[F:28])[O-:32];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2068}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-5.149","depth":0,"reaction":{"label":">>0","id":0,"pathId":11},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0029944181442260742,\"rxn_id\":\"ord-e0b0f01cfc8846efa4465e6a5288872d\",\"index\":23488,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (1.5 g, 2.96 mmol), 4-(3-hydroxypropyl)morpholine (0.623 mL, 4.5 mmol), triphenylphosphine (1.18 g, 4.5 mmol), and dichloromethane (50 mL) was added diisopropyl azodicarboxylate (0.886 mL, 4.5 mmol). The mixture was stirred at room temperature for 16 h, monitored by LCMS. After removal of solvent, the crude mixture was separated by flash column chromatography (silica), eluting with 5% methanol in dichloromethane to give N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N\\u2032-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (890 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.36 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.83 (m, 1H), 7.64 (m, 2H), 7.57 (s, 1H), 7.44 (m, 3H), 7.18 (t, 2H), 4.27 (m, 2H), 3.99 (s, 3H), 3.61 (m, 6H), 2.40 (m, 4H), 2.01 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.3.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9970055818557739,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:37][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:36][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1\",\"yield_000\":47.5},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CCOCC\",\"distance\":0.003035128116607666,\"rxn_id\":\"ord-fab5133cf99a4d628c51ef65011713b7\",\"index\":182883,\"rxn_smiles\":\"CCCCP(CCCC)CCCC.CCOCC.COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O.ClCCl.O=C(N=NC(=O)N1CCCCC1)N1CCCCC1.OCCN1CCSCC1>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"procedure_details\":\"4-(2-Hydroxyethyl)thiomorpholine (114 mg, 0.78 mmol), (J. Am. Chem. Soc. 1934. 56, 1720), in methylene chloride (1 ml) followed by 1,1\\u2032-(azodicarbonyl)dipiperidine (525 mg. 2.08 mmol) were added to a stirred solution of 4-(4-chloro-2-fluoroanilino)7-hydroxy-6 methoxyquinazoline (225 mg, 0.70 mmol), (prepared as described for the starting material in Example 2), and tributylphosphine (0.51 ml, 2.08 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours and allowed to stand for a further 18 hours. Ether (8 ml) was added, the precipitate removed by filtration and the solvent removed from the filtrate by evaporation. The residue was dissolved in acetone and ethereal hydrogen chloride (2.5 m! of a 1M solution) added. The precipitated product was collected by filtration and purified by column chromatography eluting with methylene chloride\\/methanol\\/aqueous ammonia (150\\/8\\/1). The purified product was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazoline (70 mg, 22%) as a pale yellow solid.\",\"reactant_000\":\"OCCN1CCSCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O\",\"rxn_time\":3.5,\"reactant_003\":null,\"similarity\":0.9969648718833923,\"agent_000\":\"CCCCP(CCCC)CCCC\",\"agent_001\":\"O=C(N=NC(=O)N1CCCCC1)N1CCCCC1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][S:7][CH2:6][CH2:5]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40](O)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([O:1][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][S:7][CH2:6][CH2:5]4)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1\",\"yield_000\":22.3},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0032836198806762695,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9967163801193237,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0037235617637634277,\"rxn_id\":\"ord-ae2e2a15cfb44e3c8c0bddafaf4489b5\",\"index\":501292,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O.OCCc1ccncc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"procedure_details\":\"To a solution of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea (0.1 g, 0.24 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and triphenylphosphine (0.0944 g, 0.36 mmol) in 10 mL of dry THF was added diisopropylazo-dicarboxylate (0.0728 g, 0.36 mmol) at ambient temperature. The mixture was stirred for 2 hours. Next, additional triphenylphosphine (0.0944 g, 0.36 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and diisopropylazodicarboxylate were added and the reaction mixture further stirred at room temperature overnight. The solvent from the reaction mixture was evaporated and the crude residue was dissolved in 5.0 mL of DMSO and purified by RP-HPLC. The proper fractions were collected and concentrated to ¼ volume. The aqueous solution was neutralized with 1N NaOH and extracted with ethyl acetate (2×, 59 mL). The organic layer was dried with sodium sulfate, filtered and evaporated to dryness to afford 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyridin-4-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea as a brown solid in 44% yield. LCMS m\\/z (%)=526 (M+H 79Br, 100), 528 (M+H 81Br, 67). 1H NMR (DMSO-d6) δ: 9.33 (bs, 1H), 9.24 (bs, 1H), 8.39 (dd, J=4.44 and 1.48 Hz, 2H), 7.63 (d, J=7.28 Hz, 1H), 7.59 (s, 1H), 7.56 (dd, J=8.94 and 2.71 Hz, 2H), 7.48 (m, 1H), 7.34 (d, J=2.67, 1H), 7.31 (d, J=2.67, 1H), 7.28 (dd, J=6.88 and 4.87 Hz, 2H), 7.14 (d, J=9.05 Hz, 1H), 7.09 (d, J=5.93 Hz, 1H), 4.01-4.2 (m, 2H), 3.48 (s, 3H), 2.96-2.91 (m, 2H).\",\"reactant_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCc1ccncc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9962764382362366,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"rxn_str\":\"[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[OH:14].O[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[O:14][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1\",\"yield_000\":44.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0038225650787353516,\"rxn_id\":\"ord-33bfcf35bf734b52b59d70aa5d195f4f\",\"index\":462262,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Diethyl azodicarboxylate (2.67 ml, 17 mmol) was added dropwise to a solution of 3-morpholinopropan-1-ol (1.54 g, 10 mmol), 7-hydroxy-3,4-dihydro-6-methoxy-3-((pivaloyloxy)methyl)quinazolin-4-one (2.6 g, 8.5 mmol) and triphenylphosphine (4.45 g, 17 mmol) in methylene chloride (40 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride\\/methanol (97\\/3 followed by 95\\/5) to give 3,4-dihydro-6-methoxy-3-((pivaloyloxy)metyl)-7-(3-morpholinopropoxy)quinazolin-4-one (3.6 g, 97%).\",\"reactant_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961774349212646,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]1.O[C:24]1[CH:33]=[C:32]2[C:27]([C:28](=[O:42])[N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[N:31]2)=[CH:26][C:25]=1[O:43][CH3:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:44][O:43][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:24]=1[O:22][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[N:31]=[CH:30][N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]2=[O:42]\",\"yield_000\":97.7}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":11}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":11}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":11}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":11}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.42,"id":154,"pathId":11}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":11}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":11}],"RXN":"[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[OH:17])[N+:19](=[O:21])[O-:20])[Cl:3])[F:5].[CH2:25]1[CH2:26][O:27][CH2:28][CH2:29][N:24]1[CH2:30][CH2:31][CH2:32]O>C(C)CCP(CCCC)CCCC.ClCCl.C1CN(CCC1)C(N=NC(N2CCCCC2)=O)=O>[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:32][CH2:31][CH2:30][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[N+:19](=[O:21])[O-:20])[Cl:3])[F:5];1.7.7;Mitsunobu"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":11}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":11}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":11}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-5.272","depth":0,"reaction":{"label":">>0","id":0,"pathId":1851},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1851}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1851}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1851}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1851}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1851}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1851}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1851}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1851}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1851}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1851}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-5.298","depth":0,"reaction":{"label":">>0","id":0,"pathId":330},"children":[{"depth":1,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":330}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":330}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":330}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":330}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":330}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":330}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":330}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":330}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":330}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":330}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":330}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-5.47","depth":0,"reaction":{"label":">>0","id":0,"pathId":3},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":5,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":3}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":3}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":3}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":3}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":3}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":3}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":3}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":3}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":3}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":3}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-5.722","depth":0,"reaction":{"label":">>0","id":0,"pathId":290},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":290}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":290}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":290}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":290}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":290}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":290}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":290}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":290}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":290}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":290}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-5.783","depth":0,"reaction":{"label":">>0","id":0,"pathId":227},"children":[{"depth":1,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002493739128112793,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975062608718872,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.00285494327545166,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971450567245483,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.002886652946472168,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971133470535278,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003403782844543457,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9965962171554565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003649115562438965,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.996350884437561,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"LR ALL>>28","id":28},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006411254405975342,\"rxn_id\":\"ord-73de563950e54f3a8a473ab1f9c7e3c2\",\"index\":86652,\"rxn_smiles\":\"CN(C)C=O.O.O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12.OCC1CC1.[H-].[Na+]>>O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"procedure_details\":\"Cyclopropylmethyl alcohol (0.921 ml, 11.4 mmol) was added to a stirring suspension of NaH (455 mg, 11.4 mmol) in DMF (20 ml) under an argon atmosphere. The resulting solution was allowed to stir at RT for 20 min. 6-chloro-7-fluoro-8-nitro-9H-β-carboline (500 mg, 1.9 mmol) was added to the stirring solution and the resulting mixture was allowed to stir at RT. Upon addition of H2O, a brown solid precipitated out which was filtered to give the desired 6-chloro-7-cyclopropylmethyoxy-8-nitro-9H-β-carboline (510 mg, 85%). 1H-NMR (300 MHz, DMSO-d6): δ 0.35 (m, 2H), 0.59 (m, 2H), 1.32 (m, 1H), 4.04 (d, 2H), 8.21 (d, 1H), 8.46 (d, 1H), 8.90 (s, 1H), 9.02 (s, 1H), 12.32 (b, 1H). Retention Time (LC, method: ammonium acetate standard): 2.63 min. MS (M+H+): 318.\",\"reactant_000\":\"O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12\",\"reactant_002\":null,\"reactant_001\":\"OCC1CC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9935887455940247,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1F)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1[O:5][CH2:4][CH:1]1[CH2:3][CH2:2]1)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1\",\"yield_000\":84.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006817042827606201,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9931829571723938,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.007981956005096436,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9920180439949036,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00798940658569336,\"rxn_id\":\"ord-e13729e09b02453d8b2ae8502f41e869\",\"index\":593117,\"rxn_smiles\":\"CC(C)(C)[O-].CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-].OCC(F)F.[K+]>>CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"procedure_details\":\"The subtitle compound is prepared from N-(4-bromophenyl)-2-fluoro-4-methylamino-5-nitro-benzamide, 2,2-difluoroethanol and KOtBu in analogy to example 1e.\",\"reactant_000\":\"CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9920105934143066,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2F)=[CH:4][CH:3]=1.[F:23][CH:24]([F:27])[CH2:25][OH:26].CC([O-])(C)C.[K+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2[O:26][CH2:25][CH:24]([F:27])[F:23])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008773088455200195,\"rxn_id\":\"ord-c07b2acbc69f47289d653f004b6d071c\",\"index\":64408,\"rxn_smiles\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12.Cl.OCC(F)F.[H-].[Na+]>>COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"procedure_details\":\"Sodium hydride (1.21 g, 30 mmol, as a 60% suspension in mineral oil) was charged into a round bottom flask equipped with magnetic stirring and a nitrogen blanket, washed twice with 10 mL hexanes, dried of residual hexanes under a nitrogen stream, and suspended in 1,2-dimethoxyethane (20 mL). After cooling in an ice bath to about 10° C., 2-fluoro-6-trifluoromethyl-N-(5, 8-di-methoxy[ 1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide (4.21 g, about 98.5% purity, 10 mmol) was added over about 5 min, rinsing in with 1 mL 1,2-dimethoxyethane. A slight exotherm to about 13° C. occurred. Continued ice bath cooling lowered temperature to about 6° C. over about 10 min. To the off-white suspension was added 2,2-difluoroethanol (0.815 niL, 13 mmol) over about 5 min. A slight exotherm to about 13° C. occurred. The light tan suspension was stirred at about 5-10° C. for about 1 hr, then the ice bath was removed. The temperature peaked at about 28° C. (about 2° C. above room temperature) about 0.5 hr later. The tan suspension was stirred overnight (about 20 hr total reaction time), then worked up by addition of the reaction mixture over about 7 min into 5% hydrochloric acid (80 mL, 112 mmol) at about 5-10° C. with ice bath cooling. The suspension was stirred about 18 min at about 9° C., then filtered, washed twice with 15 mL water each, washed twice with 15 mL methanol each, air-dried for about 2 hr, and finally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide to afford the product as a white powder (4.34 g, about 92.8% purity, 8.3 mmol, about 83% yield).\",\"reactant_000\":\"OCC(F)F\",\"reactant_002\":null,\"reactant_001\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9912269115447998,\"agent_000\":\"Cl\",\"agent_001\":\"[H-]\",\"agent_002\":\"[Na+]\",\"temperature\":10.0,\"product_000\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"rxn_str\":\"[H-].[Na+].F[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15].[F:31][CH:32]([F:35])[CH2:33][OH:34].Cl>>[F:31][CH:32]([F:35])[CH2:33][O:34][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:11])([F:12])[F:13])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15]\",\"yield_000\":83.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>228","id":228},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.0052683353424072266,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9947316646575928,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005525708198547363,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944742918014526,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.005835771560668945,\"rxn_id\":\"ord-6569ee74ee084f45aee0cc6bab387a3a\",\"index\":556261,\"rxn_smiles\":\"BrBr.CC(=O)O.Nc1ccc2nc(C(F)(F)F)[nH]c2c1>>Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"procedure_details\":\"To a solution of 3.2 g (16 mmol) of 2-trifluoromethyl-5-aminobenzimidazole in 50 ml of AcOH was added 0.34 ml (6.6 mmol) of Br2 dropwise and resulting reaction mixture was stirred for 1 h at 25° C. The reaction mixture was concentrated in vacuo and purified on silica gel column chromatography (10% MeOH\\/CHCl3) to yield 1.7 g (6.2 mmol, 94%) of the desired product.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.994164228439331,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"rxn_str\":\"[F:1][C:2]([F:14])([F:13])[C:3]1[NH:4][C:5]2[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[Br:15]Br>CC(O)=O>[F:14][C:2]([F:1])([F:13])[C:3]1[NH:4][C:5]2[C:11]([Br:15])=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1\",\"yield_000\":93.9},{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.005841076374053955,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994158923625946,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005856215953826904,\"rxn_id\":\"ord-1d443c1852a24a44bc10d8df0c32bd94\",\"index\":784164,\"rxn_smiles\":\"BrBr.ClC(Cl)Cl.Nc1ccc2ncsc2c1>>Nc1ccc2ncsc2c1Br\",\"procedure_details\":\"To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67 mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27 mmol) in CHCl3 (10 ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5:1) to give 7-bromobenzo[d]thiazol-6-amine (80 mg, 80%).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncsc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941437840461731,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ncsc2c1Br\",\"rxn_str\":\"[S:1]1[C:5]2[CH:6]=[C:7]([NH2:10])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Br:11]Br>C(Cl)(Cl)Cl>[Br:11][C:6]1[C:5]2[S:1][CH:2]=[N:3][C:4]=2[CH:9]=[CH:8][C:7]=1[NH2:10]\",\"yield_000\":129.3}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>528","id":528},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":227}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":227}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.3,"id":159,"pathId":227}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.3,"id":522,"pathId":227}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CUHXEXBIVQEVJM","smiles":"[O-][N+](=O)C1=CC2=C(N=CN=C2NC2=CC(Cl)=C(F)C=C2)C(Br)=C1F","intrinsicScore":0.33,"id":528,"pathId":227}],"RXN":"[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([cH:11][c:3]3[n:2][cH:1][n:23]2)[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22].[Br:24]Br>>[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([c:11]([c:3]3[n:2][cH:1][n:23]2)[Br:24])[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22];10.1.1;Bromination"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.33,"id":43,"pathId":227}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"JWFJQOCJPWGBQR","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C(Br)=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1","intrinsicScore":0.71,"id":228,"pathId":227}],"RXN":"[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])F)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>>[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":227}],"RXN":"[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:26])[F:30]>>[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:26])[F:30];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":227}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":227}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":227}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-5.815","depth":0,"reaction":{"label":">>0","id":0,"pathId":1501},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1501}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1501}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":1501}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":1501}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":1501}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1501}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1501}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1501}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1501}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1501}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-6.013","depth":0,"reaction":{"label":">>0","id":0,"pathId":0},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002089381217956543,\"rxn_id\":\"ord-8b1771262c5e44ada19659657c7eb43e\",\"index\":412829,\"rxn_smiles\":\"C=CC(=O)O.Nc1cccc(Sc2ccnc(Cl)n2)c1>>C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"procedure_details\":\"In a procedure analogous to Example 15, reaction of 3-(2-chloropyrimidin-4-ylthio)benzenamine (300 mg, 1.26 mmol) and acrylic acid (173 μL, 2.52 mmol) furnished the product (250 mg, 68%).\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9979106187820435,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"rxn_str\":\"[Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH2:15])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:16](O)(=[O:19])[CH:17]=[CH2:18]>>[Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1\",\"yield_000\":68.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0028356313705444336,\"rxn_id\":\"ord-7f4e5cc36887435cbbdc295e9f320425\",\"index\":760420,\"rxn_smiles\":\"C=CC(=O)O.Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1>>C=CC(=O)Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"procedure_details\":\"In a procedure analogous to Example 15, reaction of N1-(4-(pyridin-2-ylthio)pyrimidin-2-yl)benzene-1,3-diamine (35 mg, 0.12 mmol) and acrylic acid (16 μL, 0.24 mmol) furnished the product (18 mg, 43%).\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971643686294556,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=2)[N:9]=1.[C:22](O)(=[O:25])[CH:23]=[CH2:24]>>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:16]=[C:17]([NH:21][C:22](=[O:25])[CH:23]=[CH2:24])[CH:18]=[CH:19][CH:20]=2)[N:9]=1\",\"yield_000\":42.9},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.003855884075164795,\"rxn_id\":\"ord-4094429492154f2dbcefff644399bdf5\",\"index\":480696,\"rxn_smiles\":\"C=CC(=O)O.CCN=C=NCCCN(C)C.CN(C)C=O.Cl.Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"procedure_details\":\"To a solution of 6-amino-4-[(3-bromophenyl)amino]-quinazoline (2.0 g, 6.35 mmol) in dry DMF (20 mL) under N2 was added acrylic acid (12.7 mmol, 0.87 mL). The resulting solution was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl) (7.62 mmol, 1.46 g) was added. The reaction was stirred at 0° C. for 15 minutes and then allowed to warm to room temperature and stirred for a further 2 hours, after which additional acrylic acid (0.30 mL) and EDCI·HCL (0.30 g) were added. After a further 2 hours, the reaction was complete by tlc, solvent was removed under reduced pressure, and the resulting residue diluted with saturated NaHCO3 and repeatedly extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Column chromatography on grade III alumina eluting with EtOAc\\/MeOH (95:5) followed by recrystallization from EtOAc\\/hexane gave a spongy white solid, which upon several hours under high vacuum gave N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.06 g, 45%) as a cream powder, mp 258-261° C.\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961441159248352,\"agent_000\":\"CCN=C=NCCCN(C)C\",\"agent_001\":\"Cl\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1.[C:20](O)(=[O:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:20](=[O:23])[CH:21]=[CH2:22])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:18]=[CH:17][CH:16]=1\",\"yield_000\":45.2},{\"solvent_000\":\"CO\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.004208207130432129,\"rxn_id\":\"ord-bf24e611fd8c4b079f2ff4859f73f6ab\",\"index\":267419,\"rxn_smiles\":\"C=CC(=O)O.CCN=C=NCCCN(C)C.CN(C)C=O.CO.Cl.Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1>>C=CC(=O)Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"procedure_details\":\"To an ice-cold solution of 0.158 g (0.5 mM) of 7-amino-4-(3-bromoanilino)-quinazoline [J Med Chem, 1995:3482] and 0.108 g of acrylic acid in 5.0 mL of dry dimethylformamide (DMF) was added 0.288 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (EDAC). After stirring for 5 minutes, the mixture became a solution, and the ice bath was removed. The reaction continued to stir at room temperature for 3 hours. The reaction was then poured into a mixture of ice and water and made basic with the addition of a saturated solution of sodium bicarbonate. This aqueous mixture was extracted three times with ethyl acetate, and the pooled extracts were dried over magnesium sulfate. The solution was filtered and concentrated in vacuo to afford a light yellow solid. The solid was dissolved in 100 mL of methanol, filtered, and concentrated in vacuo to approximately 10 mL. The solid which precipitated from solution was collected and dried in vacuo at 80° C. to give 50 mg of N-[4-(3-bromo-phenylamino)-quinazolin-7-yl]acrylamide, mp >265° C. Chemical ionization mass spectra: m\\/e 369.\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9957917928695679,\"agent_000\":\"CCN=C=NCCCN(C)C\",\"agent_001\":\"Cl\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:20](O)(=[O:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CO>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:6]2[C:5]3[C:10](=[CH:11][C:2]([NH:1][C:20](=[O:23])[CH:21]=[CH2:22])=[CH:3][CH:4]=3)[N:9]=[CH:8][N:7]=2)[CH:18]=[CH:17][CH:16]=1\",\"yield_000\":27.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005647420883178711,\"rxn_id\":\"ord-61eb981de9364aeabae366904ba61a35\",\"index\":735541,\"rxn_smiles\":\"C=CC(=O)O.NCc1ccc(Sc2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)cc1>>C=CC(=O)NCc1ccc(Sc2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)cc1\",\"procedure_details\":\"In a procedure analogous to Example 15, reaction of 4-(4-(aminomethyl)phenylthio)-N-(4-morpholinophenyl)pyrimidin-2-amine (70 mg, 0.18 mmol) and acrylic acid (19 mg, 0.27 mmol) furnished the product (22 mg, 27%).\",\"reactant_000\":\"NCc1ccc(Sc2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)cc1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9943525791168213,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)NCc1ccc(Sc2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)cc1\",\"rxn_str\":\"[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[CH:19][CH:18]=3)[N:11]=2)=[CH:5][CH:4]=1.[C:29](O)(=[O:32])[CH:30]=[CH2:31]>>[O:26]1[CH2:25][CH2:24][N:23]([C:20]2[CH:21]=[CH:22][C:17]([NH:16][C:12]3[N:11]=[C:10]([S:9][C:6]4[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:8][CH:7]=4)[CH:15]=[CH:14][N:13]=3)=[CH:18][CH:19]=2)[CH2:28][CH2:27]1\",\"yield_000\":27.3}]","literatureScore":1,"label":"TTL T5 ALL>>18","id":18},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002383708953857422,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976162910461426,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003282904624938965,\"rxn_id\":\"ord-932b5c36f87f4c22a3f990aa243237aa\",\"index\":473088,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1cc(C(F)(F)F)ccc1-n1cccn1>>Nc1cc(C(F)(F)F)ccc1-n1cccn1\",\"procedure_details\":\"Method C3 was used 1-(2-nitro-4-(trifluoromethyl)phenyl)-1H-pyrazole (1.80 g, 7.00 mmol) in EtOH (40 mL) to give 760 mg (48%) of the title compound as white crystals after crystallization from hexane.\",\"reactant_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)ccc1-n1cccn1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.996717095375061,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(C(F)(F)F)ccc1-n1cccn1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:5]=1[N:14]1[CH:18]=[CH:17][CH:16]=[N:15]1)([O-])=O>CCO>[N:14]1([C:5]2[CH:6]=[CH:7][C:8]([C:10]([F:11])([F:12])[F:13])=[CH:9][C:4]=2[NH2:1])[CH:18]=[CH:17][CH:16]=[N:15]1\",\"yield_000\":47.8},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003292381763458252,\"rxn_id\":\"ord-7de54c87901942a88632590dd9ce8f67\",\"index\":398334,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc(Cl)c(Cl)cc1-n1cccc1>>Nc1cc(Cl)c(Cl)cc1-n1cccc1\",\"procedure_details\":\"A stirred solution of 42.4 g (0.165 mole) of 1-(4,5-dichloro-2-nitrophenyl)pyrrole in 730 ml. of tetrahydrofuran and 365 ml. of water is treated according to the manipulative procedure described above in Example 13(b) to give 1-(2-amino-4,5-dichlorophenyl)pyrrole, m.p. 57°-58° C.\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Cl)cc1-n1cccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9967076182365417,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Cl)cc1-n1cccc1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N:9]2[CH:13]=[CH:12][CH:11]=[CH:10]2)=[C:4]([N+:14]([O-])=O)[CH:3]=1.O1CCCC1>O>[NH2:14][C:4]1[CH:3]=[C:2]([Cl:1])[C:7]([Cl:8])=[CH:6][C:5]=1[N:9]1[CH:13]=[CH:12][CH:11]=[CH:10]1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0033306479454040527,\"rxn_id\":\"ord-cc5be6ff04be4cdfab0f091cda8d88ed\",\"index\":597934,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(OCC2CC2)cc1C(F)(F)F>>Nc1ccc(OCC2CC2)cc1C(F)(F)F\",\"procedure_details\":\"Stannous chloride (4.75 g, 21 mmol) was added to a solution of 4-cyclopropylmethoxy-1-nitro-2-trifluoromethylbenzene (1.1 g, 4.2 mmol) in ethanol (12 mL). The reaction temperature was raised to 70° C. for 1.5 hour. The reaction mixture was concentrated in vacuo and the residue dissolved in ethyl acetate (20 mL). Water (15 mL) was added and sodium hydrogen carbonate was added until pH 7. The mixture was filtered and the organic phase collected. The aqueous phase was extracted with ethyl acetate (20 mL). The combined organic phases were dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (38 g) using heptane and ethyl acetate (9:1) as eluent to give 0.49 g of 4-cyclopropylmethoxy-2-trifluoromethylphenylamine.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCC2CC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.996669352054596,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"Nc1ccc(OCC2CC2)cc1C(F)(F)F\",\"rxn_str\":\"[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[C:8]([C:15]([F:18])([F:17])[F:16])[CH:7]=2)[CH2:3][CH2:2]1>C(O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([NH2:12])=[C:8]([C:15]([F:16])([F:17])[F:18])[CH:7]=2)[CH2:3][CH2:2]1\",\"yield_000\":50.5},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":null,\"distance\":0.0033327341079711914,\"rxn_id\":\"ord-cc629b913bd347bda79dd567222e9d5b\",\"index\":531041,\"rxn_smiles\":\"CCOC(C)=O.O=[N+]([O-])c1cc(N2CCOCC2)ccc1N1CCOCC1>>Nc1cc(N2CCOCC2)ccc1N1CCOCC1\",\"procedure_details\":\"To a stirred solution of 4-(4-morpholino-3-nitrophenyl)morpholine (5600 mg, 19 mmol) in EtOAc was added stannous chloride, dihydrate (18 g, 95 mmol). The reaction was stirred at rt for 10 min and at reflux for 90 min. After this time LC\\/MS shows desired product. The reaction was cooled to rt and the precipitate was collected and washed with aq. 1N sodium hydroxide solution, water and brine and dried under vacuum overnight. After this time the solid was dissolved in EtOAc and washed with aq. 1N sodium hydroxide solution and brine, dried, filtered and evaporated in vacuo to give desired product. The filtrate was diluted with EtOAc (300 mL) and washed with aq. sodium hydroxide and brine, dried over magnesium sulfate, filtered and evaporated in vacuo to give additional desired product.\",\"reactant_000\":\"O=[N+]([O-])c1cc(N2CCOCC2)ccc1N1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.9966672658920288,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1cc(N2CCOCC2)ccc1N1CCOCC1\",\"rxn_str\":\"[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:9][C:8]=2[N+:19]([O-])=O)[CH2:3][CH2:2]1>CCOC(C)=O>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[CH:9][C:8]=2[NH2:19])[CH2:3][CH2:2]1\",\"yield_000\":null}]","literatureScore":1,"label":"T5 CF ER AT UA ALL>>95","id":95},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0024016499519348145,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9975983500480652,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0034421682357788086,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9965578317642212,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005340635776519775,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9946593642234802,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005926012992858887,\"rxn_id\":\"ord-61db4d46573641b09a365452241e4a72\",\"index\":23563,\"rxn_smiles\":\"C1CCOC1.CCc1nc2cc(F)ccc2[n+]([O-])n1.O.OCCCN1CCOCC1.[H-].[Na+]>>CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"procedure_details\":\"NaH (60% dispersion in oil, 310 mg, 7.75 mmol) was added to dry THF (10 mL) and stirred at 20° C. for 20 min prior to the addition of 3-(4-morpholinyl)propanol (676 mg, 4.66 mmol). The mixture was stirred for 30 min, fluoride 28 (300 mg, 1.55 mmol) added and the resulting solution stirred at 20° C. for 2.5 h under N2. Water was added and the solution extracted with DCM (4×30 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by column chromatography, eluting with a gradient (0-5%) MeOH\\/DCM to give 1-oxide 31 (257 mg, 52%) as a pale yellow solid, mp 108-111° C.; 1H NMR δ 8.33 (d, J=9.3 Hz, 1 H, H-8), 7.21-7.26 (m, 2 H, H-7 and H-5), 4.22 (t, J=6.4 Hz, 2 H, CH2), 3.73 (t, J=4.6 Hz, 4 H, 2×CH2O), 3.00 (q, J=7.6 Hz, 2 H, CH2), 2.55 (t, J=7.0 Hz, 2 H, CH2), 2.48 (t, J=4.6 Hz, 4 H, 2×CH2N), 2.06 (m, 2 H, CH2), 1.43 (t, J=7.6 Hz, 3 H, CH3); 13C NMR δ 168.7, 164.6, 150.3, 128.4, 123.1, 121.6, 106.3, 67.3 (2), 66.9, 55.1, 53.7 (2), 30.7, 26.0, 12.2. Anal. Calcd for C16H22N4O3: C, 60.4; H, 7.0; N, 17.6. Found: C, 60.4; H, 7.0; N, 17.4%.\",\"reactant_000\":\"CCc1nc2cc(F)ccc2[n+]([O-])n1\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9940739870071411,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"rxn_str\":\"[H-].[Na+].C1COCC1.[N:8]1([CH2:14][CH2:15][CH2:16][OH:17])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27](F)=[CH:26][C:24]=2[N:25]=1)[CH3:19]>O>[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27]([O:17][CH2:16][CH2:15][CH2:14][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:26][C:24]=2[N:25]=1)[CH3:19]\",\"yield_000\":52.1},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005959570407867432,\"rxn_id\":\"ord-a73cb883fae1487ca599634bf5ed7e4b\",\"index\":602333,\"rxn_smiles\":\"C1CCOC1.NS(=O)(=O)c1ncccc1F.OCCF.[H-].[Na+]>>NS(=O)(=O)c1ncccc1OCCF\",\"procedure_details\":\"5.76 ml of 2-fluoroethanol are added dropwise, with cooling, to a suspension of 6.54 g of sodium hydride (55.6% NaH in oil) in 120 ml of tetrahydrofuran so that the temperature does not exceed 20° C. When the dropwise addition is complete, the reaction mixture is stirred at room temperature for 15 minutes and then a further solution of 10.56 g of 3-fluoro-pyrid-2-ylsulfonamide in 60 ml of tetrahydrofuran is added dropwise over a period of 10 minutes. The reaction solution is then stirred for 10 minutes at room temperature and for 2 hours at reflux before it is cooled and concentrated. For purification, the oil remaining is chromatographed on a silica gel column using ethyl acetate\\/hexane 4\\/1. Evaporation of the eluant yields a light-coloured oil which crystallises spontaneously, yielding 5.88 g of title product which melts at 122°-123° C.\",\"reactant_000\":\"OCCF\",\"reactant_002\":null,\"reactant_001\":\"NS(=O)(=O)c1ncccc1F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9940404295921326,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NS(=O)(=O)c1ncccc1OCCF\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][OH:4].[H-].[Na+].F[C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1>O1CCCC1>[F:1][CH2:2][CH2:3][O:4][C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1\",\"yield_000\":null}]","literatureScore":1,"label":"UA T5 AT LR TTL ALL>>166","id":166},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":5,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":0}]},{"depth":5,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":0}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.71,"id":460,"pathId":0}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.34,"id":43,"pathId":0}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"ZYHSNOOGZFKYJT","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1OCCCN1CCOCC1","intrinsicScore":0.57,"id":166,"pathId":0}],"RXN":"[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])F)[n:3][cH:2][n:1][c:13]2[Cl:14].[CH2:15]1[CH2:16][O:17][CH2:18][CH2:19][N:20]1[CH2:21][CH2:22][CH2:23][OH:24]>>[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])[O:24][CH2:23][CH2:22][CH2:21][N:20]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[n:3][cH:2][n:1][c:13]2[Cl:14];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OAASLEYJLYELJM","smiles":"NC1=C(OCCCN2CCOCC2)C=C2N=CN=C(Cl)C2=C1","intrinsicScore":0.76,"id":95,"pathId":0}],"RXN":"[cH:8]1[c:5]2[c:4]([cH:12][c:11]([c:9]1[N+:10](=O)[O-])[O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[n:3][cH:2][n:1][c:6]2[Cl:7]>>[cH:8]1[c:5]2[c:4]([cH:12][c:11]([c:9]1[NH2:10])[O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[n:3][cH:2][n:1][c:6]2[Cl:7];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.76,"id":6,"pathId":0}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"FEYMOAFHQQUUMQ","smiles":"ClC1=NC=NC2=C1C=C(NC(=O)C=C)C(OCCCN1CCOCC1)=C2","intrinsicScore":0.051,"id":18,"pathId":0}],"RXN":"[CH2:2]=[CH:1][C:3](=[O:4])O.[cH:18]1[c:19]2[c:25]([cH:26][c:15]([c:16]1[NH2:17])[O:14][CH2:13][CH2:12][CH2:11][N:6]3[CH2:5][CH2:10][O:9][CH2:8][CH2:7]3)[n:24][cH:23][n:22][c:20]2[Cl:21]>>[CH2:2]=[CH:1][C:3](=[O:4])[NH:17][c:16]1[cH:18][c:19]2[c:25]([cH:26][c:15]1[O:14][CH2:13][CH2:12][CH2:11][N:6]3[CH2:5][CH2:10][O:9][CH2:8][CH2:7]3)[n:24][cH:23][n:22][c:20]2[Cl:21];2.1.2;Carboxylic"},{"depth":1,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":0}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":0}],"RXN":"[CH2:13]=[CH:12][C:11](=[O:14])[NH:10][c:9]1[cH:15][c:5]2[c:6]([cH:7][c:8]1[O:16][CH2:17][CH2:18][CH2:19][N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[n:1][cH:2][n:3][c:4]2Cl.[cH:29]1[cH:28][c:27]([c:33]([cH:32][c:30]1[NH2:31])[Cl:34])[F:26]>P(C1=C2C(=CC=C1)C(C)(C)C3=CC=CC(=C3O2)P(C4=CC=CC=C4)C5=CC=CC=C5)(C6=CC=CC=C6)C7=CC=CC=C7.O=C(/C=C/C1=CC=CC=C1)/C=C/C2=CC=CC=C2.[O-]C(=O)[O-].[Cs+].[Pd]>[CH2:13]=[CH:12][C:11](=[O:14])[NH:10][c:9]1[cH:15][c:5]2[c:6]([cH:7][c:8]1[O:16][CH2:17][CH2:18][CH2:19][N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[n:1][cH:2][n:3][c:4]2[NH:31][c:30]4[cH:29][cH:28][c:27]([c:33]([cH:32]4)[Cl:34])[F:26];1.3.7;Chloro"},{"pathScore":"-6.362","depth":0,"reaction":{"label":">>0","id":0,"pathId":162},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.6,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.008023500442504883,\"rxn_id\":\"ord-42dc5bd007e148f297483fd574a84112\",\"index\":514864,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCN(CC)CC.Cl.Cl.N#Cc1ccc(Cn2cncc2CCN)cc1F>>N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride (0.92 g, 0.0029 mmol) in acetonitrile (150 mL) and triethylamine (3.2 mL) was added 2-bromoethyl ether (0.839 mL, 0.0067 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in uacuo and the residue was dissolved in EtOAc which was washed twice with 1M HCl (100 mL). The HCl layers were combined and adjusted to pH=9 with solid Na2CO3 and extraxcted 3 times with EtOAc. The EtOAc layers were combined and dried with brine and MgSO4. Removal of the EtOAc in vacuo yielded the title compound which was used as is in the next step.\",\"reactant_000\":\"N#Cc1ccc(Cn2cncc2CCN)cc1F\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919764995574951,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=2)[CH:9]=[N:8][CH:7]=1.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>C(#N)C.C(N(CC)CC)C>[F:20][C:14]1[CH:13]=[C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][N:3]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:7][N:8]=[CH:9]2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.008291244506835938,\"rxn_id\":\"ord-08bb54aa0ab244ff90317c31f9d4c5e8\",\"index\":731783,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.NC1CCN(Cc2ccccc2)CC1.O=C([O-])[O-].[K+].[K+]>>c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"procedure_details\":\"To a stirred mixture of 4-amino-1-benzylpiperidine (1.53 mL, 7.5 mmol), K2CO3 (2.28 g, 16.5 mmol) and DMF (15 mL) heated at 50° C. was added dropwise over 60 min bis(2-bromoethyl) ether (0.96 mL, 7.65 mmol). After stirring for 6 hours at 80° C., the solvent was removed by blowing with a stream of nitrogen over 2 hours. The residue was purified on a silica gel column to give 1.7 g (87%) of 4-(1-benzyl-piperidin-4-yl)morpholine as a waxy solid.\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"NC1CCN(Cc2ccccc2)CC1\",\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9917087554931641,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"rxn_str\":\"[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>CN(C=O)C>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:1]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1\",\"yield_000\":87.1},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.008305191993713379,\"rxn_id\":\"ord-ac7a693c46694fd5b13039f5c104d79e\",\"index\":134482,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N.O=C([O-])[O-].[K+].[K+]>>CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"procedure_details\":\"cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane\\/methanol\\/ammonia 100:0:0->140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m\\/e=403.3 [(M+H)+].\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9916948080062866,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"rxn_str\":\"[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]\",\"yield_000\":68.6},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.00859677791595459,\"rxn_id\":\"ord-aa3eb88c8e6c445794e16d41429514f0\",\"index\":719114,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O.CCN(CC)CC.Cl.Cl>>CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-2-methyl-imidazol-1-ylmethyl]-2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile dihydrochloride (as described in Example 11) (0.25 g, 0.456 mmol) in acetonitrile (35.0 mL) and triethylamine (1.8 mL) was added 2-bromoethyl ether (0.133 mL, 1.06 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in vacuo to obtain the title compound after purification by preparative HPLC.\",\"reactant_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9914032220840454,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]4([CH2:36][CH3:37])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]4=[O:35])[CH:22]=3)[CH:13]=2)[C:9]([CH3:38])=[N:8][CH:7]=1.Br[CH2:40][CH2:41][O:42][CH2:43][CH2:44]Br>C(#N)C.C(N(CC)CC)C>[CH2:36]([C:27]1([C:23]2[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=2)[O:20][C:14]2[CH:13]=[C:12]([CH2:11][N:10]3[C:6]([CH2:5][CH2:4][N:3]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[CH:7][N:8]=[C:9]3[CH3:38])[CH:19]=[CH:18][C:15]=2[C:16]#[N:17])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]1=[O:35])[CH3:37]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.008690357208251953,\"rxn_id\":\"ord-90e436a959164d40ab8c094946564425\",\"index\":740936,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.Nc1ccc(Br)c(Cl)c1.O.O=C([O-])[O-].[I-].[K+].[K+].[K+]>>Clc1cc(N2CCOCC2)ccc1Br\",\"procedure_details\":\"4-Bromo-3-chloroaniline (500 mg) was dissolved in DMF (10 ml), and bis(2-bromoethyl)ether (1.12 g), K2CO3 (1.34 g), and potassium iodide (80 mg) were added thereto, followed by stirring at 80° C. for 2 days. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 20% EtOAc\\/hexane) to obtain 4-(4-bromo-3-chlorophenyl)morpholine (263 mg).\",\"reactant_000\":\"Nc1ccc(Br)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":48.0,\"reactant_003\":null,\"similarity\":0.991309642791748,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[I-]\",\"agent_002\":\"[K+]\",\"temperature\":80.0,\"product_000\":\"Clc1cc(N2CCOCC2)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:9].Br[CH2:11][CH2:12][O:13][CH2:14][CH2:15]Br.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][C:3]=1[Cl:9]\",\"yield_000\":39.3}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":\"CCO\",\"distance\":0.0034121274948120117,\"rxn_id\":\"ord-c978110d0ebb47c5ab077decdb013eb8\",\"index\":750238,\"rxn_smiles\":\"CCO.CP(C)C.[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1.[NH4+].[OH-].c1ccncc1>>NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"procedure_details\":\"To a solution of (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 0.230 mmol) in pyridine (2 mL) was added NH4OH (200 μl) and trimethylphosphine (344 μl, 0.344 mmol) sequentially at room temperature. The reaction mixture was stirred for 2 h. After EtOH (1 mL) was added, the reaction mixture was concentrated in vacuo. The crude product was purified by flash chromatography (20% MeOH in DCM containing 0.5% NH3\\/DCM) to provide 89.6 mg of (S)\\u2014N-(2-amino-1-(3-chloro-5-fluorophenyl)ethyl)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamide (79%). LCMS (m\\/z): 488.2 (MH+), 0.66 min. 1H NMR (500 MHz, METHANOL-d4) δ ppm 7.98-7.89 (m, 1H), 7.89-7.79 (m, 1H), 7.74 (td, J=1.4, 8.0 Hz, 1H), 7.69-7.61 (m, 1H), 7.41-7.28 (m, 1H), 7.27-7.08 (m, 2H), 5.27-5.12 (m, 1H), 4.07 (dd, J=3.8, 11.0 Hz, 2H), 3.69-3.52 (m, 2H), 3.14-3.03 (m, 2H), 2.96 (tt, J=3.9, 11.7 Hz, 1H), 2.02-1.77 (m, 4H).\",\"reactant_000\":\"[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996587872505188,\"agent_000\":\"CP(C)C\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]([C:14]2[CH:35]=[CH:34][C:17]([C:18]([NH:20][C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=3)[CH2:22][N:23]=[N+]=[N-])=[O:19])=[C:16]([F:36])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[NH4+].[OH-].CP(C)C.CCO>N1C=CC=CC=1>[NH2:23][CH2:22][C@@H:21]([NH:20][C:18](=[O:19])[C:17]1[CH:34]=[CH:35][C:14]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([CH:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:4]=2)=[CH:15][C:16]=1[F:36])[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=1\",\"yield_000\":79.8},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004088282585144043,\"rxn_id\":\"ord-042249e7216a47579d0f62148c807cd2\",\"index\":714256,\"rxn_smiles\":\"C1CCOC1.C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21>>NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"procedure_details\":\"20 μL of a 1M trimethylphosphine\\/tetrahydrofuran solution was added to 6 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-azidoethyl) ester dissolved in a mixture of 0.15 mL of tetrahydrofuran and 0.02 mL of water at room temperature, and the mixture was stirred for 13 hours. After the solvent was distilled under reduced pressure, the residue was purified by reverse phase column chromatography (Wako gel 50C18 (made by Wako Pure Chemical Industries Ltd.), eluent: water to a 50% aqueous solution of acetonitrile), and the obtained solids were further washed with tetrahydrofuran, thereby yielding 2 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-aminoethyl)ester.\",\"reactant_000\":\"[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":13.0,\"reactant_003\":null,\"similarity\":0.995911717414856,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"rxn_str\":\"CP(C)C.O1CCCC1.[N:10]([CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17])=[N+]=[N-]>O1CCCC1.O>[NH2:10][CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17]\",\"yield_000\":35.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0043354034423828125,\"rxn_id\":\"ord-d978c1c7e23041a1b604dc1dd6ff7a6f\",\"index\":562746,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1>>NCc1cncc(C#Cc2ccccc2)c1\",\"procedure_details\":\"To a solution of 3-(azidomethyl)-5-(phenylethynyl)pyridine (7.8 g, 33.3 mmol) in tetrahydrofuran (101 mL) at 0° C. was added trimethylphosphine (1M in tetrahydrofuran, 49.9 mL, 49.9 mmol). After evolution of nitrogen had slowed, the ice bath was removed and stirring continued for 1 h. To this was added water (6.0 mL, 333 mmol) and the mixture stirred at room temperature for 2 h. The reaction was concentrated, dissolved in ether, washed with water (5×), then brine, dried over potassium carbonate, filtered, and concentrated to give 5.96 g (77%) as a faint yellow solid which was used without purification. 1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H)1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H). 13C NMR (CDCl3) δ: 150.8, 147.9, 137.8, 137.4, 131.8, 128.9, 128.6, 122.7, 120.3, 92.7, 86.1, 43.7. Mass spec.: 209.1 (MH)+.\",\"reactant_000\":\"[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9956645965576172,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCc1cncc(C#Cc2ccccc2)c1\",\"rxn_str\":\"[N:1]([CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[N+]=[N-].CP(C)C.O>O1CCCC1>[C:13]1([C:12]#[C:11][C:9]2[CH:10]=[C:5]([CH2:4][NH2:1])[CH:6]=[N:7][CH:8]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.005223870277404785,\"rxn_id\":\"ord-089f68b08fe543bfbdedd8c9521524ae\",\"index\":377104,\"rxn_smiles\":\"C1COCCO1.CP(C)C.O.[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21>>NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"procedure_details\":\"Azide 23 (Example 10, 100 mg, 0.23 mmol) is dissolved in 0.9 mL of 1,4-dioxane\\/H2O (8:1), and 0.3 mL of a trimethylphospine solution (1 M in THF) is added. The reaction is stirred at room temperature for 3 h, then all volatiles are removed in vacuo. The crude product is purified by flash column chromatography with dichloromethane\\/methanol (95:5 to 10:1). Yield: 87 mg (0.021 mmol, 91%).\",\"reactant_000\":\"[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9947761297225952,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"rxn_str\":\"[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][N:14]=[N+]=[N-])=[C:4]([O:17][CH2:18][C:19]2[CH:32]=[CH:31][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)[N:3]=1.CP(C)C>O1CCOCC1.O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][NH2:14])=[C:4]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:27])([F:29])[F:28])=[CH:31][CH:32]=2)[N:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.005546689033508301,\"rxn_id\":\"ord-be83b62c5d5249cf938c714d7117d666\",\"index\":193745,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1>>NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"procedure_details\":\"To a solution of (S)-2-[[1-(2-azidoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid (6.28 g, 12.11 mmol) in THF (91 mL) was added a solution of trimethylphosphine in THF (48.5 mL, 48.46 mmol, 1.0M) at 0° C. It was a clear solution in the beginning and after 30 min some precipitate was formed and this mixture was stirred for overnight at which time TLC analysis of the mixture indicated the absence of starting material. Then, 10 equiv. of water (120 mmol, 2.16 mL) was added and the mixture was stirred for 2 h at room temperature. The solvent was removed under vacuum and the residue was azeotrophed two times with toluene to give a pasty material which was purified using HPLC to obtain 4.57 g (77% yield) of (S)-2-[[1-(2-aminoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid as an amorphous white solid. ES(+)-HRMS m\\/e calcd. for C24H27Cl2N3O4 (M+H)+ 492.1452, obsd. 492.1451.\",\"reactant_000\":\"[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9944533109664917,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"rxn_str\":\"[N:1]([CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:21][CH:20]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:23][CH:24]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1\",\"yield_000\":76.6}]","literatureScore":1,"label":"TTL ALL>>167","id":167},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008967578411102295,\"rxn_id\":\"ord-cf2e4e3955c04b01a2130e020e40723c\",\"index\":264007,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-4-fluorophenylamine (1.67 g, 4.87 mmoles) and sodium azide (0.38 g, 5.84 mmoles) in DMSO (20 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (1.44 g, 4.14 mmoles).\",\"reactant_000\":\"Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9910324215888977,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([O:18][CH2:19][CH2:20]Cl)[C:12]=2[NH2:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>CS(C)=O.O>[N:23]([CH2:20][CH2:19][O:18][C:13]1[CH:14]=[C:15]([F:17])[CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:22])=[N+:24]=[N-:25]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CCOC(C)=O\",\"distance\":0.00959622859954834,\"rxn_id\":\"ord-693a2494d2a64d6e84f87595007867e9\",\"index\":765833,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc(OCCCCl)cc1CO.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"procedure_details\":\"DMF (7.5 mL) was added to (5-(3-chloropropoxy)-2-nitrophenyl)methanol (635 mg, 0.00258 moles) and sodium azide (252 mg, 0.00387 moles) in a flask, and the resulting mixture was heated to 70° C. and stirred overnight. The reaction was diluted in ethyl acetate (100 mL) and washed twice with water (75 mL each) and once with brine (75 mL). The organic layer was dried with anhydrous magnesium sulfate, which was filtered out. The filtrate was concentrated on a rotary evaporator and dried in vacuo overnight to yield (5-(3-azidopropoxy)-2-nitrophenyl)methanol as a yellow solid (yield 88%). H NMR (400 MHz, CD2Cl2) δ 8.16 (d, J=9.1 Hz, 1H), 7.27 (d, J=2.8 Hz, 1H), 6.91 (dd, J=9.1, 2.8 Hz, 1H), 4.98 (s, 2H), 4.18 (t, J=6.0 Hz, 2H), 3.53 (t, J=6.6 Hz, 2H), 2.12-2.06 (m, 2H). 13C-NMR (100 MHz, CD2Cl2) δ 163.99, 141.22, 128.43, 114.97, 113.93, 66.15, 63.26, 48.68, 29.13 HRMS m\\/z: calculated for C10H12N4O4 [M+H]+, 253.0931. found, 253.0939.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCCCCl)cc1CO\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9904037714004517,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"rxn_str\":\"CN(C=O)C.Cl[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>C(OCC)(=O)C>[N:22]([CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1)=[N+:23]=[N-:24]\",\"yield_000\":88.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CS(C)=O\",\"distance\":0.009707868099212646,\"rxn_id\":\"ord-ed6541dc83464b24a92f34950c9068d0\",\"index\":137604,\"rxn_smiles\":\"CS(C)=O.O.O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"procedure_details\":\"A mixture of 6-(2-chloro-ethoxy)-3-(naphthalene-1-sulfonyl)-1-H-indazole (0.19 g, 0.5 mmoles) and sodium azide (0.04 g, 0.62 mmoles) in DMSO (2 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.17 g, 0.45 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9902921319007874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1.[N-:27]=[N+:28]=[N-:29].[Na+]>CS(C)=O.O>[N:27]([CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1)=[N+:28]=[N-:29]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.010035336017608643,\"rxn_id\":\"ord-dc8e8747d9b6443687f6f629e49ca7d3\",\"index\":120480,\"rxn_smiles\":\"CN(C)C=O.Nc1ncnc2c1ncn2CCCCl.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"procedure_details\":\"A mixture of 9-(3-chloropropyl)adenine and sodium azide in DMF was stirred at 80° C. for 24 hours, cooled to room temperature and filtered. The solid was washed with CH2Cl2. The solvent was removed from the combined filtrates and the residue was taken up in water with sonication. The aqueous layer was extracted with CH2Cl2. After removing the solvent, the crude product was recrystallized from ethanol to give 9-(3-azidopropyl)adenine as a white crystalline solid.\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1ncnc2c1ncn2CCCCl\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9899646639823914,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14].[N-:15]=[N+:16]=[N-:17].[Na+]>CN(C=O)C>[N:15]([CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14])=[N+:16]=[N-:17]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.010115861892700195,\"rxn_id\":\"ord-5c4de244180f41a2bbc87a484238a728\",\"index\":335449,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-phenylamine (0.5 g, 1.53 mmoles) and sodium azide (0.15 g, 2.29 mmoles) in DMSO (10 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.39 g, 1.17 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9898841381072998,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19]Cl)[C:12]=2[NH2:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>CS(C)=O.O>[N:22]([CH2:19][CH2:18][O:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:21])=[N+:23]=[N-:24]\",\"yield_000\":null}]","literatureScore":0.99,"label":"ER UA TTL ALL>>672","id":672},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":162}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":162}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":162}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":162}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.6,"id":165,"pathId":162}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL>>990","id":990},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"JUINSXZKUKVTMD","smiles":"N=[N+]=[N-]","intrinsicScore":0.6,"id":990,"pathId":162}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"FCEJYNJLOZLCCR","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1OCCCN=[N+]=[N-]","intrinsicScore":0.3,"id":672,"pathId":162}],"RXN":"[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4]Cl)[N+:27](=[O:28])[O-:29])[Cl:24])[F:21].[NH:3]=[N+:1]=[N-:2]>>[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4][N:3]=[N+:1]=[N-:2])[N+:27](=[O:28])[O-:29])[Cl:24])[F:21];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NGGHYTSBRHGJPA","smiles":"NCCCOC1=C(C=C2C(NC3=CC=C(F)C(Cl)=C3)=NC=NC2=C1)[N+]([O-])=O","intrinsicScore":0.051,"id":167,"pathId":162}],"RXN":"[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][N:20]=[N+]=[N-])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27]>C1CCOC1.C(OCC)(C)=O.CP(C)C.O>[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][NH2:20])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27];9.7.13;Azido"},{"depth":3,"reaction":{"label":"TTL ALL>>51","id":51},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"FOZVXADQAHVUSV","smiles":"BrCCOCCBr","intrinsicScore":0.051,"id":51,"pathId":162}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":162}],"RXN":"[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][NH2:8])[N+:30](=[O:31])[O-:32])[Cl:29])[F:26].[CH2:2]([CH2:1]Br)[O:3][CH2:4][CH2:5]Br>N#CC.[O-]C(=O)[O-].[I-].[K+]>[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][N:8]4[CH2:1][CH2:2][O:3][CH2:4][CH2:5]4)[N+:30](=[O:31])[O-:32])[Cl:29])[F:26];4.2.5;Morpholine"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":162}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":162}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":162}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-6.462","depth":0,"reaction":{"label":">>0","id":0,"pathId":730},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":730}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":730}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":730}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":730}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":730}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":730}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":730}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":730}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":730}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":730}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":730}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-6.473","depth":0,"reaction":{"label":">>0","id":0,"pathId":695},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":695}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":695}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":695}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":695}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":695}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":695}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":695}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":695}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":695}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":695}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":695}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-6.499","depth":0,"reaction":{"label":">>0","id":0,"pathId":713},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":713}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":713}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":713}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":713}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":713}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":713}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":713}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":713}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":713}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":713}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":713}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-6.543","depth":0,"reaction":{"label":">>0","id":0,"pathId":77},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.005186200141906738,\"rxn_id\":\"ord-d1fa20d56e464afca9b17e9c52f114e7\",\"index\":450278,\"rxn_smiles\":\"CCCCO.CCOC(=O)c1ccc(-c2cc3c(Cl)ncnc3[nH]2)cc1.Nc1ccc(F)c(Cl)c1>>CCOC(=O)c1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3[nH]2)cc1\",\"procedure_details\":\"3.6 g (12 mmol) 4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-benzoic acid ethyl ester (WO 97\\/02266) are suspended in 80 ml n-butanol and treated with 3.5 g (24 mmol) 3-chloro-4-fluoro-aniline. The mixture is heated to 145° C. under stirring. After 30 min a clear brown solution is obtained which turns into a thick suspension after 2 h. After a total of 3 h the reaction mixture is cooled in an ice bath and the product collected by filtration; m.p.>300° C.; Rf(dichloromethane\\/ethanol 95:5 plus 1% conc. ammonia)=0.29; HPLC tR=11.66 min.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1ccc(-c2cc3c(Cl)ncnc3[nH]2)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9948137998580933,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":145.0,\"product_000\":\"CCOC(=O)c1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3[nH]2)cc1\",\"rxn_str\":\"[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:14]3[N:15]=[CH:16][N:17]=[C:18](Cl)[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)[CH3:2].[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>C(O)CCC>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:26][C:25]4[CH:27]=[CH:28][C:29]([F:30])=[C:23]([Cl:22])[CH:24]=4)[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.005290091037750244,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947099089622498,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"CC(C)(C)O\",\"distance\":0.0053021907806396484,\"rxn_id\":\"ord-5510c71cc19244ccb4d87f14f34e8de5\",\"index\":424079,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"procedure_details\":\"To a solution of 4-chloro-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine (40 mg, 0.15 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 1 ml) was added 3-chloro-4-fluoroaniline (22 mg, 0.15 mmol). The mixture was heated at 90° C. for 2 days. After cooling down to room temperature, the solvents were removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 100:1) to yield the title compound as a white solid (28 mg, 50%).\",\"reactant_000\":\"Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9946978092193604,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[CH:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":49.9},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.005939364433288574,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9940606355667114,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.006047487258911133,\"rxn_id\":\"ord-110ea862e79f4175b380aaf2573b8840\",\"index\":333623,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Cl)c12.CCN(C(C)C)C(C)C.Nc1ccc(F)c(Cl)c1>>CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Nc3ccc(F)c(Cl)c3)c12\",\"procedure_details\":\"The crude tert-butyl (2R)-2-({[7-(benzyloxy)-4-chloroquinazolin-5-yl]oxy}methyl)-pyrrolidine-1-carboxylate was taken up in THF (5 ml) and 3-chloro-4-fluoroaniline (160 mg) and N,N-diisopropylethylamine (580 μl) were each added in one portion and the solution was heated at 70° C. for 18 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo to leave a thick brown oil. Purification by flash chromatography, using 1.5% methanol in DCM as eluent, gave the tert-butyl (2R)-2-[({7-(benzyloxy)-4-[3-chloro-4-fluoroanilino]quinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate as a beige foam (350 mg, 54% over 2 steps); Mass spectrum MH+ 481.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Cl)c12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9939525127410889,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Nc3ccc(F)c(Cl)c3)c12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](Cl)=[N:14][CH:15]=[N:16]2)=[C:11]([O:20][CH2:21][C@H:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:34][C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][C:41]=1[F:42])[NH2:38].C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:38][C:37]3[CH:39]=[CH:40][C:41]([F:42])=[C:35]([Cl:34])[CH:36]=3)=[N:14][CH:15]=[N:16]2)=[C:11]([O:20][CH2:21][C@H:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0024016499519348145,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9975983500480652,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0034421682357788086,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9965578317642212,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005340635776519775,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9946593642234802,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005926012992858887,\"rxn_id\":\"ord-61db4d46573641b09a365452241e4a72\",\"index\":23563,\"rxn_smiles\":\"C1CCOC1.CCc1nc2cc(F)ccc2[n+]([O-])n1.O.OCCCN1CCOCC1.[H-].[Na+]>>CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"procedure_details\":\"NaH (60% dispersion in oil, 310 mg, 7.75 mmol) was added to dry THF (10 mL) and stirred at 20° C. for 20 min prior to the addition of 3-(4-morpholinyl)propanol (676 mg, 4.66 mmol). The mixture was stirred for 30 min, fluoride 28 (300 mg, 1.55 mmol) added and the resulting solution stirred at 20° C. for 2.5 h under N2. Water was added and the solution extracted with DCM (4×30 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by column chromatography, eluting with a gradient (0-5%) MeOH\\/DCM to give 1-oxide 31 (257 mg, 52%) as a pale yellow solid, mp 108-111° C.; 1H NMR δ 8.33 (d, J=9.3 Hz, 1 H, H-8), 7.21-7.26 (m, 2 H, H-7 and H-5), 4.22 (t, J=6.4 Hz, 2 H, CH2), 3.73 (t, J=4.6 Hz, 4 H, 2×CH2O), 3.00 (q, J=7.6 Hz, 2 H, CH2), 2.55 (t, J=7.0 Hz, 2 H, CH2), 2.48 (t, J=4.6 Hz, 4 H, 2×CH2N), 2.06 (m, 2 H, CH2), 1.43 (t, J=7.6 Hz, 3 H, CH3); 13C NMR δ 168.7, 164.6, 150.3, 128.4, 123.1, 121.6, 106.3, 67.3 (2), 66.9, 55.1, 53.7 (2), 30.7, 26.0, 12.2. Anal. Calcd for C16H22N4O3: C, 60.4; H, 7.0; N, 17.6. Found: C, 60.4; H, 7.0; N, 17.4%.\",\"reactant_000\":\"CCc1nc2cc(F)ccc2[n+]([O-])n1\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9940739870071411,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"rxn_str\":\"[H-].[Na+].C1COCC1.[N:8]1([CH2:14][CH2:15][CH2:16][OH:17])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27](F)=[CH:26][C:24]=2[N:25]=1)[CH3:19]>O>[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27]([O:17][CH2:16][CH2:15][CH2:14][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:26][C:24]=2[N:25]=1)[CH3:19]\",\"yield_000\":52.1},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005959570407867432,\"rxn_id\":\"ord-a73cb883fae1487ca599634bf5ed7e4b\",\"index\":602333,\"rxn_smiles\":\"C1CCOC1.NS(=O)(=O)c1ncccc1F.OCCF.[H-].[Na+]>>NS(=O)(=O)c1ncccc1OCCF\",\"procedure_details\":\"5.76 ml of 2-fluoroethanol are added dropwise, with cooling, to a suspension of 6.54 g of sodium hydride (55.6% NaH in oil) in 120 ml of tetrahydrofuran so that the temperature does not exceed 20° C. When the dropwise addition is complete, the reaction mixture is stirred at room temperature for 15 minutes and then a further solution of 10.56 g of 3-fluoro-pyrid-2-ylsulfonamide in 60 ml of tetrahydrofuran is added dropwise over a period of 10 minutes. The reaction solution is then stirred for 10 minutes at room temperature and for 2 hours at reflux before it is cooled and concentrated. For purification, the oil remaining is chromatographed on a silica gel column using ethyl acetate\\/hexane 4\\/1. Evaporation of the eluant yields a light-coloured oil which crystallises spontaneously, yielding 5.88 g of title product which melts at 122°-123° C.\",\"reactant_000\":\"OCCF\",\"reactant_002\":null,\"reactant_001\":\"NS(=O)(=O)c1ncccc1F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9940404295921326,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NS(=O)(=O)c1ncccc1OCCF\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][OH:4].[H-].[Na+].F[C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1>O1CCCC1>[F:1][CH2:2][CH2:3][O:4][C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1\",\"yield_000\":null}]","literatureScore":1,"label":"UA T5 AT LR TTL ALL>>166","id":166},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":5,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":77}]},{"depth":5,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":77}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.71,"id":460,"pathId":77}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.34,"id":43,"pathId":77}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ZYHSNOOGZFKYJT","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":166,"pathId":77}],"RXN":"[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])F)[n:3][cH:2][n:1][c:13]2[Cl:14].[CH2:15]1[CH2:16][O:17][CH2:18][CH2:19][N:20]1[CH2:21][CH2:22][CH2:23][OH:24]>>[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])[O:24][CH2:23][CH2:22][CH2:21][N:20]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[n:3][cH:2][n:1][c:13]2[Cl:14];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.024,"id":19,"pathId":77}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":77}],"RXN":"[cH:27]1[cH:26][c:24]([c:31]([cH:30][c:28]1[NH2:29])[Cl:32])[F:25].[cH:11]1[c:10]2[c:5]([cH:4][c:3]([c:12]1[N+:13](=[O:15])[O-:14])[O:2][CH2:1][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[n:6][cH:7][n:8][c:9]2Cl>>[cH:27]1[cH:26][c:24]([c:31]([cH:30][c:28]1[NH:29][c:9]2[c:10]3[cH:11][c:12]([c:3]([cH:4][c:5]3[n:6][cH:7][n:8]2)[O:2][CH2:1][CH2:16][CH2:17][N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[N+:13](=[O:15])[O-:14])[Cl:32])[F:25];1.3.7;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":77}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":77}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":77}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-6.581","depth":0,"reaction":{"label":">>0","id":0,"pathId":698},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":698}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":698}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":698}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":698}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":698}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":698}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":698}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":698}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":698}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":698}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":698}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-6.729","depth":0,"reaction":{"label":">>0","id":0,"pathId":44},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6.1,"literature":"[{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.0024762749671936035,\"rxn_id\":\"ord-9206c31e495e40198c626776f18ebc3a\",\"index\":585159,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COC(=O)[C@@H](C)[C@@H]1CCc2cc(O)ccc21.O.O=C([O-])[O-].[Cs+].[Cs+]>>COC(=O)[C@@H](C)[C@@H]1CCc2cc(OCCCBr)ccc21\",\"procedure_details\":\"Methyl (2S)-2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1 yl]propanoate (Example 14) (500 mg, 2.27 mmol), dibromopropane (4.308 g, 21.34 mmol), Cs2CO3 (834 mg, 2.56 mmol), and water (5 drops) were combined in DMF (20 mL) and stirred for 7 h at rt. The reaction mixture was concentrated under reduced pressure, water was added and the aqueous solution was extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc\\/hexane (v\\/v)=1:25) gave 263 mg (34%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 1.08 (d, 3H), 1.91 (m, 1H), 2.17 (m, 1H), 2.32 (m, 2H), 2.80 (m, 1H), 2.88 (m, 2H), 3.51 (m, 1H), 3.61 (t, 2H), 3.72 (s, 3H), 4.08 (t, 2H), 6.69 (d, 1H), 6.76 (s, 1H), 6.98 (d, 1H).\",\"reactant_000\":\"O=C([O-])[O-]\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"COC(=O)[C@@H](C)[C@@H]1CCc2cc(O)ccc21\",\"rxn_time\":7.0,\"reactant_003\":null,\"similarity\":0.9975237250328064,\"agent_000\":\"[Cs+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COC(=O)[C@@H](C)[C@@H]1CCc2cc(OCCCBr)ccc21\",\"rxn_str\":\"[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([C@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])[CH2:6][CH2:5]2.Br[C:18]([Br:21])([CH3:20])C.[C:22]([O-])([O-])=O.[Cs+].[Cs+]>O.CN(C=O)C>[Br:21][CH2:18][CH2:20][CH2:22][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([C@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])[CH2:6][CH2:5]2\",\"yield_000\":34.0},{\"solvent_000\":\"CCC(C)=O\",\"solvent_001\":null,\"distance\":0.0033658742904663086,\"rxn_id\":\"ord-53aae8a75c18456fa8b709f87e828e9f\",\"index\":589545,\"rxn_smiles\":\"CC(C)(Br)Br.CCC(C)=O.O=C([O-])[O-].Oc1ccc2c(c1)oc1cc(Cl)ccc12.[K+].[K+]>>Clc1ccc2c(c1)oc1cc(OCCCBr)ccc12\",\"procedure_details\":\"A mixture of 98.4 g (0.45 mole) of 7-chlorodibenzofuran-3-ol, 200 ml of methyl ethyl ketone, 93 g (0.67 mole) of potassium carbonate and 283 g (1.4 moles) of dibromopropane was refluxed for 24 hours. The inorganic precipitate was filtered off with suction and the filtrate was concentrated under reduced pressure. The residue was dissolved in 500 ml of methylene chloride and the solution was washed with 100 ml of water, 100 ml of 2 N sodium hydroxide solution and 100 ml of water in succession, dried over sodium sulfate and concentrated under reduced pressure. The solid residue was left to stand with 30 ml of pentane at 0° C. for 30 minutes, filtered off with suction and washed with 30 ml of cold n-pentane. 77 g of pure 1-bromo-3-(7-chlorodibenzofuran-3-oxy)-propane of melting point 83°-85° C. were obtained; yield: 50% of theory.\",\"reactant_000\":\"CC(C)(Br)Br\",\"reactant_002\":\"Oc1ccc2c(c1)oc1cc(Cl)ccc12\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9966341257095337,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Clc1ccc2c(c1)oc1cc(OCCCBr)ccc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:15]=[CH:14][C:5]2[C:6]3[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:7]=3[O:8][C:4]=2[CH:3]=1.[C:16](=O)([O-])[O-].[K+].[K+].Br[C:23]([Br:26])([CH3:25])C>C(C(C)=O)C>[Br:26][CH2:23][CH2:25][CH2:16][O:13][C:10]1[CH:11]=[CH:12][C:6]2[C:5]3[CH:14]=[CH:15][C:2]([Cl:1])=[CH:3][C:4]=3[O:8][C:7]=2[CH:9]=1\",\"yield_000\":50.4},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.003755807876586914,\"rxn_id\":\"ord-ad00632e1f604c52987b8464b6586244\",\"index\":429960,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COc1ccc(-c2cc(=O)c3ccc(O)cc3o2)cc1OC.O=C([O-])[O-].[Br-].[K+].[K+].[K+]>>COc1ccc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc1OC\",\"procedure_details\":\"This compound (61) was prepared from 3\\u2032,4\\u2032-dimethoxy-7-hydroxy-flavone, 27 (3 g, 10 mmol), dibromo propane (4 mL, 39.2 mmol) and potassium carbonate (2.8 g, 20 mmol) in dry dimethyl formamide (150 mL) using the identical procedure as described for 56. Yield 3.4 g (80%); mp 148-149° C.; MS (FAB) 419\\/421 (M++1); IR (KBr) 1630; 1H NMR (200 MHz, CDCl3) δ 8.12 (d, J=9.5 Hz, 1H), 7.53 (dd, J=8.5 Hz, 2.0 Hz, 1H), 7.36 (d, J=1.9 Hz, 1H), 6.99-6.95 (m, 3H), 6.68 (s, 1H), 4.24 (t, J=5.8 Hz, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 3.64 (t, J=6.3 Hz, 2H), 2.39 (q, J=6.1 Hz, 2H).\",\"reactant_000\":\"COc1ccc(-c2cc(=O)c3ccc(O)cc3o2)cc1OC\",\"reactant_002\":\"O=C([O-])[O-]\",\"reactant_001\":\"CC(C)(Br)Br\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962441921234131,\"agent_000\":\"[Br-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc1OC\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:6]1[O:7][C:8]2[C:13]([C:14](=[O:16])[CH:15]=1)=[CH:12][CH:11]=[C:10]([OH:17])[CH:9]=2.Br[C:24]([Br:27])([CH3:26])C.[C:28](=O)([O-])[O-].[K+].[K+].[K+].[Br-]>CN(C)C=O>[Br:27][CH2:24][CH2:26][CH2:28][O:17][C:10]1[CH:9]=[C:8]2[C:13]([C:14](=[O:16])[CH:15]=[C:6]([C:5]3[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:3]([O:2][CH3:1])[CH:4]=3)[O:7]2)=[CH:12][CH:11]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.0038167834281921387,\"rxn_id\":\"ord-8f37b80150c343f895cd5a9ba6cd0eb8\",\"index\":711891,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COc1cc(-c2cc(=O)c3ccc(O)cc3o2)cc(OC)c1OC.O=C([O-])[O-].[Br-].[K+].[K+].[K+]>>COc1cc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc(OC)c1OC\",\"procedure_details\":\"This compound (59) was prepared from 7-hydroxy-3\\u2032,4\\u2032,5\\u2032-trimethoxy-flavone, 25 (3.3 g, 10 mmol), dibromo propane (3 mL, 30 mmol) and potassium carbonate (2.7 g, 20 mmol) in dry dimethyl formamide (120 mL) using the identical procedure as described for 56. Yield 3.1 g (69%); mp 156-157° C.; MS (FAB) 449\\/451 (M++1); IR (KBr) 1629; 1H NMR (200 MHz, CDCl3) δ 8.13 (d, J=9.4 Hz, 1H), 7.11 (s, 2H), 7.01-6.97 (m, 2H), 6.70 (s, 1H), 4.25 (t, J=5.8 Hz, 2H), 3.96 (s, 6H), 3.93 (s, 3H), 3.64 (t, J=6.3 Hz, 2H), 2.39 (q, J=6.1 Hz, 2H).\",\"reactant_000\":\"COc1cc(-c2cc(=O)c3ccc(O)cc3o2)cc(OC)c1OC\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961832165718079,\"agent_000\":\"[Br-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc(OC)c1OC\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[CH:7]=[C:8]([C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[O:9]2)=[CH:4][CH:3]=1.Br[C:26]([Br:29])([CH3:28])C.[C:30](=O)([O-])[O-].[K+].[K+].[K+].[Br-]>CN(C)C=O>[Br:29][CH2:26][CH2:28][CH2:30][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[CH:7]=[C:8]([C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[O:9]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CC(=O)OC(C)C\",\"distance\":0.003999054431915283,\"rxn_id\":\"ord-6b7ff184146e44f58a563b737ef5d8b3\",\"index\":342812,\"rxn_smiles\":\"CC(=O)OC(C)C.CC(C)(Br)Br.CCCc1c(O)ccc2c(CC)noc12.CN(C)C=O.O=C([O-])[O-].[Cs+].[Cs+]>>CCCc1c(OCCCBr)ccc2c(CC)noc12\",\"procedure_details\":\"A solution of 3-ethyl-6-hydroxy-7-propylbenz[4,5]isoxazole (2.00 grams; 9.74 mmol) in dry DMF was treated with dibromopropane (7.17 mL; 38.97 mmol) and cesium carbonate (3.49 grams; 10.71 mmol). The solution was stirred at room temperature for 10 hours, then partioned between isopropyl acetate and pH 4.0 buffer. The organic layer was washed twice with water, dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel chromatography afforded the title compound (1.74 g).\",\"reactant_000\":\"CCCc1c(O)ccc2c(CC)noc12\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9960009455680847,\"agent_000\":\"[Cs+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CCCc1c(OCCCBr)ccc2c(CC)noc12\",\"rxn_str\":\"[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][C:10]([OH:15])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][N:4]=1)[CH3:2].Br[C:17]([Br:20])([CH3:19])C.[C:21](=O)([O-])[O-].[Cs+].[Cs+].C(OC(C)C)(=O)C>CN(C=O)C>[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][C:10]([O:15][CH2:21][CH2:19][CH2:17][Br:20])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][N:4]=1)[CH3:2]\",\"yield_000\":54.8}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":44}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":44}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":44}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":44}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.7,"id":154,"pathId":44}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":4,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>491","id":491},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KQNBBQSOHFVNDL","smiles":"CC(C)(O)Br","intrinsicScore":0.7,"id":491,"pathId":44}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":44}],"RXN":"CC(C)(O)Br.c1cc(c(cc1Nc2c3cc(c(cc3ncn2)O)[N+](=O)[O-])Cl)F>>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCBr)[N+](=O)[O-])Cl)F;0.0;Unrecognized"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":44}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":44}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":44}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":44}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":44}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-6.823","depth":0,"reaction":{"label":">>0","id":0,"pathId":702},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0029944181442260742,\"rxn_id\":\"ord-e0b0f01cfc8846efa4465e6a5288872d\",\"index\":23488,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (1.5 g, 2.96 mmol), 4-(3-hydroxypropyl)morpholine (0.623 mL, 4.5 mmol), triphenylphosphine (1.18 g, 4.5 mmol), and dichloromethane (50 mL) was added diisopropyl azodicarboxylate (0.886 mL, 4.5 mmol). The mixture was stirred at room temperature for 16 h, monitored by LCMS. After removal of solvent, the crude mixture was separated by flash column chromatography (silica), eluting with 5% methanol in dichloromethane to give N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N\\u2032-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (890 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.36 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.83 (m, 1H), 7.64 (m, 2H), 7.57 (s, 1H), 7.44 (m, 3H), 7.18 (t, 2H), 4.27 (m, 2H), 3.99 (s, 3H), 3.61 (m, 6H), 2.40 (m, 4H), 2.01 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.3.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9970055818557739,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:37][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:36][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1\",\"yield_000\":47.5},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CCOCC\",\"distance\":0.003035128116607666,\"rxn_id\":\"ord-fab5133cf99a4d628c51ef65011713b7\",\"index\":182883,\"rxn_smiles\":\"CCCCP(CCCC)CCCC.CCOCC.COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O.ClCCl.O=C(N=NC(=O)N1CCCCC1)N1CCCCC1.OCCN1CCSCC1>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"procedure_details\":\"4-(2-Hydroxyethyl)thiomorpholine (114 mg, 0.78 mmol), (J. Am. Chem. Soc. 1934. 56, 1720), in methylene chloride (1 ml) followed by 1,1\\u2032-(azodicarbonyl)dipiperidine (525 mg. 2.08 mmol) were added to a stirred solution of 4-(4-chloro-2-fluoroanilino)7-hydroxy-6 methoxyquinazoline (225 mg, 0.70 mmol), (prepared as described for the starting material in Example 2), and tributylphosphine (0.51 ml, 2.08 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours and allowed to stand for a further 18 hours. Ether (8 ml) was added, the precipitate removed by filtration and the solvent removed from the filtrate by evaporation. The residue was dissolved in acetone and ethereal hydrogen chloride (2.5 m! of a 1M solution) added. The precipitated product was collected by filtration and purified by column chromatography eluting with methylene chloride\\/methanol\\/aqueous ammonia (150\\/8\\/1). The purified product was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazoline (70 mg, 22%) as a pale yellow solid.\",\"reactant_000\":\"OCCN1CCSCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O\",\"rxn_time\":3.5,\"reactant_003\":null,\"similarity\":0.9969648718833923,\"agent_000\":\"CCCCP(CCCC)CCCC\",\"agent_001\":\"O=C(N=NC(=O)N1CCCCC1)N1CCCCC1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][S:7][CH2:6][CH2:5]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40](O)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([O:1][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][S:7][CH2:6][CH2:5]4)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1\",\"yield_000\":22.3},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0032836198806762695,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9967163801193237,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0037235617637634277,\"rxn_id\":\"ord-ae2e2a15cfb44e3c8c0bddafaf4489b5\",\"index\":501292,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O.OCCc1ccncc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"procedure_details\":\"To a solution of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea (0.1 g, 0.24 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and triphenylphosphine (0.0944 g, 0.36 mmol) in 10 mL of dry THF was added diisopropylazo-dicarboxylate (0.0728 g, 0.36 mmol) at ambient temperature. The mixture was stirred for 2 hours. Next, additional triphenylphosphine (0.0944 g, 0.36 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and diisopropylazodicarboxylate were added and the reaction mixture further stirred at room temperature overnight. The solvent from the reaction mixture was evaporated and the crude residue was dissolved in 5.0 mL of DMSO and purified by RP-HPLC. The proper fractions were collected and concentrated to ¼ volume. The aqueous solution was neutralized with 1N NaOH and extracted with ethyl acetate (2×, 59 mL). The organic layer was dried with sodium sulfate, filtered and evaporated to dryness to afford 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyridin-4-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea as a brown solid in 44% yield. LCMS m\\/z (%)=526 (M+H 79Br, 100), 528 (M+H 81Br, 67). 1H NMR (DMSO-d6) δ: 9.33 (bs, 1H), 9.24 (bs, 1H), 8.39 (dd, J=4.44 and 1.48 Hz, 2H), 7.63 (d, J=7.28 Hz, 1H), 7.59 (s, 1H), 7.56 (dd, J=8.94 and 2.71 Hz, 2H), 7.48 (m, 1H), 7.34 (d, J=2.67, 1H), 7.31 (d, J=2.67, 1H), 7.28 (dd, J=6.88 and 4.87 Hz, 2H), 7.14 (d, J=9.05 Hz, 1H), 7.09 (d, J=5.93 Hz, 1H), 4.01-4.2 (m, 2H), 3.48 (s, 3H), 2.96-2.91 (m, 2H).\",\"reactant_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCc1ccncc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9962764382362366,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"rxn_str\":\"[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[OH:14].O[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[O:14][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1\",\"yield_000\":44.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0038225650787353516,\"rxn_id\":\"ord-33bfcf35bf734b52b59d70aa5d195f4f\",\"index\":462262,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Diethyl azodicarboxylate (2.67 ml, 17 mmol) was added dropwise to a solution of 3-morpholinopropan-1-ol (1.54 g, 10 mmol), 7-hydroxy-3,4-dihydro-6-methoxy-3-((pivaloyloxy)methyl)quinazolin-4-one (2.6 g, 8.5 mmol) and triphenylphosphine (4.45 g, 17 mmol) in methylene chloride (40 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride\\/methanol (97\\/3 followed by 95\\/5) to give 3,4-dihydro-6-methoxy-3-((pivaloyloxy)metyl)-7-(3-morpholinopropoxy)quinazolin-4-one (3.6 g, 97%).\",\"reactant_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961774349212646,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]1.O[C:24]1[CH:33]=[C:32]2[C:27]([C:28](=[O:42])[N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[N:31]2)=[CH:26][C:25]=1[O:43][CH3:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:44][O:43][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:24]=1[O:22][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[N:31]=[CH:30][N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]2=[O:42]\",\"yield_000\":97.7}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":702}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":702}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":702}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":702}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.42,"id":154,"pathId":702}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":702}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":702}],"RXN":"[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[OH:17])[N+:19](=[O:21])[O-:20])[Cl:3])[F:5].[CH2:25]1[CH2:26][O:27][CH2:28][CH2:29][N:24]1[CH2:30][CH2:31][CH2:32]O>C(C)CCP(CCCC)CCCC.ClCCl.C1CN(CCC1)C(N=NC(N2CCCCC2)=O)=O>[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:32][CH2:31][CH2:30][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[N+:19](=[O:21])[O-:20])[Cl:3])[F:5];1.7.7;Mitsunobu"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":702}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":702}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":702}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":702}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-6.852","depth":0,"reaction":{"label":">>0","id":0,"pathId":37},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":37}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":37}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":37}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":37}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":37}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":4,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":37}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":37}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":37}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":37}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":37}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":37}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":37}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-6.889","depth":0,"reaction":{"label":">>0","id":0,"pathId":20},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":20}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":20}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":20}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":20}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":20}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":20}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":20}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":20}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":20}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":20}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":20}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":20}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-6.959","depth":0,"reaction":{"label":">>0","id":0,"pathId":40},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":40}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":40}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":40}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":40}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":40}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":40}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":40}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":40}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":40}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":40}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":40}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":40}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-6.97","depth":0,"reaction":{"label":">>0","id":0,"pathId":2094},"children":[{"depth":1,"reaction":{"scalabilityModelScore":5.2,"literature":"[{\"solvent_000\":\"ClP(Cl)Cl\",\"solvent_001\":\"ClC(Cl)Cl\",\"distance\":0.03192847967147827,\"rxn_id\":\"ord-4ee3d8d301824f80b57afcbb6894ed3d\",\"index\":186003,\"rxn_smiles\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC.ClC(Cl)Cl.ClP(Cl)Cl>>COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"procedure_details\":\"A solution of N-oxide 3 (10 mM) and phosphorus trichloride (30 mM) in anhydrous chloroform (100 ml) was refluxed for 7 h. Solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulphate and then evaporated under reduced pressure. The residue was recrystallized from isopropanol to provide the title dimethyl quinoline-2,3-dicarboxylate 7 as an off white (or light yellow) powder.\",\"reactant_000\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9680715203285217,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"rxn_str\":\"[N+:1]1([O-])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16].P(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.04028010368347168,\"rxn_id\":\"ord-2fc2b37b70194a0cb07bb83eba1a43cc\",\"index\":771709,\"rxn_smiles\":\"CC(=O)O.CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)[n+]([O-])c2)c2cc(C)oc2c1.[Fe]>>CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)nc2)c2cc(C)oc2c1\",\"procedure_details\":\"To a stirred solution of ethyl 4-({6-[(dimethylamino)carbonyl]-1-oxidopyridin-3-yl}oxy)-2-methyl-1-benzofuran-6-carboxylate (176 mg, 0.457 mmol) in 15 mL of acetic acid, was added powdered Fe while keeping the temperature at 70° C. for 2 hrs. LC-MS showed that the reaction was complete. The reaction was cooled to room temperature, and the insoluble material was filtered. The mother liquor was diluted with EtOAc, washed with NaHCO3, brine, and dried over Na2SO4, and concentrated. The crude product was introduced into a silica gel column and eluted with MeOH\\/CHCl3 (2\\/98 to 5\\/95) to provide the product (135 mg, 85% yield) as colorless oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.40 (t, J=7.16 Hz, 3H) 2.47 (s, 3 H) 3.15 (d, 6 H) 4.39 (q, J=7.03 Hz, 2 H) 6.25 (s, 1 H) 7.30 (d, J=2.45 Hz, 1 H) 7.55-7.64 (m, 1 H) 7.64-7.76 (m, 1 H) 8.00 (s, 1 H) 8.38 (s, 1 H); LC-MS (ESI)+m\\/z=369.00 (M+H)+.\",\"reactant_000\":\"CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)[n+]([O-])c2)c2cc(C)oc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9597198963165283,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)nc2)c2cc(C)oc2c1\",\"rxn_str\":\"[CH3:1][N:2]([CH3:28])[C:3]([C:5]1[N+:10]([O-])=[CH:9][C:8]([O:12][C:13]2[C:18]3[CH:19]=[C:20]([CH3:22])[O:21][C:17]=3[CH:16]=[C:15]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:14]=2)=[CH:7][CH:6]=1)=[O:4]>C(O)(=O)C.[Fe]>[CH3:28][N:2]([CH3:1])[C:3]([C:5]1[N:10]=[CH:9][C:8]([O:12][C:13]2[C:18]3[CH:19]=[C:20]([CH3:22])[O:21][C:17]=3[CH:16]=[C:15]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:14]=2)=[CH:7][CH:6]=1)=[O:4]\",\"yield_000\":80.2},{\"solvent_000\":\"ClP(Cl)Cl\",\"solvent_001\":null,\"distance\":0.043328046798706055,\"rxn_id\":\"ord-f836f0a2f3284415a2eeb6b9b08ed583\",\"index\":425996,\"rxn_smiles\":\"CCOC(=O)N1C[C@@H]2CCN(Cc3ccc(-c4c(O)[nH]c5ccc(C#N)cc45)[n+]([O-])c3)[C@@H]2C1.ClP(Cl)Cl>>CCOC(=O)N1C[C@@H]2CCN(Cc3ccc(-c4c(O)[nH]c5ccc(C#N)cc45)nc3)[C@@H]2C1\",\"procedure_details\":\"The titled compound was prepared in analogy to example 4.2 starting from 2-(5-cyano-2-hydroxy-1H-indol-3-yl)-5-(((3aS,6aS)-5-(ethoxy-carbonyl)hexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl)methyl)pyridine 1-oxide (100 mg) and phosphorus trichloride (123 mg). The obtained crude product was used without further purification in the next reaction step.\",\"reactant_000\":\"CCOC(=O)N1C[C@@H]2CCN(Cc3ccc(-c4c(O)[nH]c5ccc(C#N)cc45)[n+]([O-])c3)[C@@H]2C1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.956671953201294,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)N1C[C@@H]2CCN(Cc3ccc(-c4c(O)[nH]c5ccc(C#N)cc45)nc3)[C@@H]2C1\",\"rxn_str\":\"[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([OH:12])=[C:6]2[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[CH2:24][CH2:23][C@H:22]3[CH2:25][N:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:27][C@@H:21]23)=[CH:15][N+:14]=1[O-])#[N:2].P(Cl)(Cl)Cl>>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([OH:12])=[C:6]2[C:13]1[N:14]=[CH:15][C:16]([CH2:19][N:20]2[CH2:24][CH2:23][C@H:22]3[CH2:25][N:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:27][C@@H:21]23)=[CH:17][CH:18]=1)#[N:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.04372096061706543,\"rxn_id\":\"ord-41f86ab7b419465b93bad7cb1b735ee9\",\"index\":112985,\"rxn_smiles\":\"CC(=O)O.COc1cc[n+]([O-])c(NCCN(C(C)C)C(C)C)c1.[Fe]>>COc1ccnc(NCCN(C(C)C)C(C)C)c1\",\"procedure_details\":\"2-(2-diisopropylaminoethylamino)-4-methoxypyridine-N-oxide (4.3 g., 15 mmole) dissolved in glacial acetic acid (32 ml.) is refluxed with iron powder (8.2 g.) for three hours. The reaction mixture is filtered to remove insoluble salts and then the solvent evaporated. The residue is dissolved in methanol, treated with excess potassium hydroxide pellets and filtered to remove more insoluble salts. The concentrate solution is dissolved in chloroform, washed with water, dried over sodium sulfate, filtered through a pad of charcoal and evaporated to give oily product.\",\"reactant_000\":\"COc1cc[n+]([O-])c(NCCN(C(C)C)C(C)C)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9562790393829346,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccnc(NCCN(C(C)C)C(C)C)c1\",\"rxn_str\":\"[CH:1]([N:4]([CH:17]([CH3:19])[CH3:18])[CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][N+:9]=1[O-])([CH3:3])[CH3:2]>C(O)(=O)C.[Fe]>[CH:17]([N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][N:9]=1)([CH3:18])[CH3:19]\",\"yield_000\":null},{\"solvent_000\":\"C1=CCCCC1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.04372107982635498,\"rxn_id\":\"ord-e79e74c481414470aec1b7e2b799dffb\",\"index\":735026,\"rxn_smiles\":\"C1=CCCCC1.CC(C)O.COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1.[Pd]>>COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"procedure_details\":\"A mixture of 7-({2-[(4-methoxybenzyl)amino]-1-oxidopyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (21.1 g, 0.0502 mol), cyclohexene (100 mL, 0.9 mol) and Pd (10% on Carbon, 4.5 g) in isopropyl alcohol (400 mL, 5 mol) was heated at 85° C. overnight. Additional catalyst (2.5 g) and cyclohexene (30 mL) were added. The mixture was heated at 90° C. overnight and then filtered. The filtrate was concentrated to give 7-({2-[(4-methoxybenzyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid which was used in the next step without purification. LCMS ES+ 405.7\",\"reactant_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.956278920173645,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":85.0,\"product_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N+:10]=2[O-])=[CH:5][CH:4]=1.C(O)(C)C>[Pd].C1CCCCC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[CH:30][CH:31]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0051348209381103516,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9948651790618896,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":\"O\",\"distance\":0.006154000759124756,\"rxn_id\":\"ord-5050581a7a5447f3968e07ab51214d53\",\"index\":68216,\"rxn_smiles\":\"CC(=O)O.Nc1ccc(OC(F)(F)F)cc1-c1ncn[nH]1.O.O=C(Cl)CCl>>O=C(CCl)Nc1ccc(OC(F)(F)F)cc1-c1ncn[nH]1\",\"procedure_details\":\"To a cooled solution of 4-trifluoromethoxy-2-(2H-[1,2,4]triazol-3-yl)-phenylamine (3.00 g, 12.3 mmol) in acetic acid (62 mL) was added dropwise chloroacetyl chloride (1.96 mL, 24.6 mmol). The resulting light brown suspension was stirred for 20 h at ambient temperature and was then poured into water (246 mL) and stirred for another 3 h. The precipitate was filtered off and washed with water. Drying in vacuo afforded the title compound (3.22 g, 82%) as an off-white solid. MS: m\\/e=323.1 [M+H]+.\",\"reactant_000\":\"O=C(Cl)CCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1-c1ncn[nH]1\",\"rxn_time\":20.0,\"reactant_003\":null,\"similarity\":0.9938459992408752,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C(CCl)Nc1ccc(OC(F)(F)F)cc1-c1ncn[nH]1\",\"rxn_str\":\"[F:1][C:2]([F:17])([F:16])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([C:11]2[NH:12][N:13]=[CH:14][N:15]=2)[CH:5]=1.[Cl:18][CH2:19][C:20](Cl)=[O:21].O>C(O)(=O)C>[Cl:18][CH2:19][C:20]([NH:10][C:7]1[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:16])[F:17])=[CH:5][C:6]=1[C:11]1[NH:12][N:13]=[CH:14][N:15]=1)=[O:21]\",\"yield_000\":81.6},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0062607526779174805,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9937392473220825,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"CC(Cl)Cl\",\"solvent_001\":\"c1ccncc1\",\"distance\":0.006559848785400391,\"rxn_id\":\"ord-13c5267a6a4f49f28c25694bb40f3106\",\"index\":32284,\"rxn_smiles\":\"CC(Cl)Cl.Nc1ccc2oc3c(c2c1)CCCCCC3.O=C(Cl)CCl.c1ccncc1>>O=C(CCl)Nc1ccc2oc3c(c2c1)CCCCCC3\",\"procedure_details\":\"Following the procedure of Example 1, 6,7,8,9,10,11-Hexahydro-benzo[b]-cycloocta[d]furan-2-ylamine (0.80 g, 3.7 mmol), chloroacetyl chloride (0.31 mL, 3.9 mmol), and pyridine (0.60 mL, 7.4 mmol) in dichloroethane (25 mL) provided 2-chloro-N-6,7,8,9,10,11-hexahydrobenzo[b]cycloocta[d]furan-2-ylacetamide (1.1 g). MS (ESI) m\\/z 292 ([M+H]+).\",\"reactant_000\":\"O=C(Cl)CCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2oc3c(c2c1)CCCCCC3\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9934401512145996,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCl)Nc1ccc2oc3c(c2c1)CCCCCC3\",\"rxn_str\":\"[CH:1]1[C:9]2[C:8]3[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:7]=3[O:6][C:5]=2[CH:4]=[CH:3][C:2]=1[NH2:16].[Cl:17][CH2:18][C:19](Cl)=[O:20].N1C=CC=CC=1>ClC(Cl)C>[Cl:17][CH2:18][C:19]([NH:16][C:2]1[CH:3]=[CH:4][C:5]2[O:6][C:7]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:8]=3[C:9]=2[CH:1]=1)=[O:20]\",\"yield_000\":101.9},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.006609737873077393,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9933902621269226,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4}]","literatureScore":0.99,"label":"AT TTL ALL>>39","id":39},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":2094}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":2094}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2094}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2094}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":2094}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":2094}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":2094}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.48,"id":37,"pathId":2094}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.48,"id":70,"pathId":2094}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"IRLWIGFEJOXUIM","smiles":"[O-][N+]1=CN=C(NC2=CC=C(F)C(Cl)=C2)C2=C1C=C(OCCCN1CCOCC1)C(NC(=O)CCCl)=C2","intrinsicScore":0.024,"id":39,"pathId":2094}],"RXN":"[cH:31]1[cH:32][c:33]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:24][c:25]3[n+:26]([cH:28][n:29]2)[O-:27])[O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[NH2:30])[Cl:35])[F:36].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:31]1[cH:32][c:33]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:24][c:25]3[n+:26]([cH:28][n:29]2)[O-:27])[O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[NH:30][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:36];2.1.1;Amide"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2094}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCCN4CCOCC4)NC(=O)CCCl)Cl)F>O1CCCC1.CCO.O.[Cl-].[Fe].[NH4+]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2094}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-6.972","depth":0,"reaction":{"label":">>0","id":0,"pathId":1021},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1021}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1021}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":1021}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":1021}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":1021}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":1021}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":1021}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":1021}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":1021}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":1021}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1021}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1021}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-6.996","depth":0,"reaction":{"label":">>0","id":0,"pathId":23},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":23}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":23}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":23}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":23}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":23}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":23}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":23}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":23}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":23}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":23}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":23}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":23}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.026","depth":0,"reaction":{"label":">>0","id":0,"pathId":283},"children":[{"depth":1,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005404233932495117,\"rxn_id\":\"ord-76225eb83f1d49a69b3350dfc5ea5286\",\"index\":160606,\"rxn_smiles\":\"COc1cc(-c2nc3ccc(O)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC.ClCCCN1CCCCC1>>COc1cc(-c2nc3ccc(OCCCN4CCCCC4)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC\",\"procedure_details\":\"The title compound was prepared by reacting the compound of Example 104 with 3-(piperidin-1-yl)propyl chloride essentially as previously described mp 138° C., IR, NMR, MS. 584\",\"reactant_000\":\"ClCCCN1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(-c2nc3ccc(O)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945957660675049,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(-c2nc3ccc(OCCCN4CCCCC4)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC\",\"rxn_str\":\"[F:1][C:2]([F:33])([F:32])[C:3]1[CH:31]=[CH:30][CH:29]=[CH:28][C:4]=1[CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([OH:15])[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=1.[N:34]1([CH2:40][CH2:41][CH2:42]Cl)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:31]=[CH:30][CH:29]=[CH:28][C:4]=1[CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([O:15][CH2:42][CH2:41][CH2:40][N:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C:16]1[CH:17]=[C:18]([O:26][CH3:27])[C:19]([O:24][CH3:25])=[C:20]([O:22][CH3:23])[CH:21]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.0063250064849853516,\"rxn_id\":\"ord-3166dd898c594256b3d4f5254941b7f6\",\"index\":764054,\"rxn_smiles\":\"CN(C)C=O.ClCCCN1CCCC1.O=C1NCCc2ccc(O)cc21>>O=C1NCCc2ccc(OCCCN3CCCC3)cc21\",\"procedure_details\":\"7-(3-Pyrrolidin-1-yl-propoxy)-3,4-dihydro-2H-isoquinolin-1-one is prepared from 7-hydroxy-3,4-dihydro-2H-isoquinolin-1-one (0.48 g, 2.94 mmol) in a manner substantially analogous to Procedure A except DMF is used in place of dioxane and 1-(3-Chloro-propyl)-pyrrolidine is used instead of N-(3-chloropropyl)piperidine. Following aqueous workup, the crude material is purified by flash chromatography (Biotage 40M SiO2, elute 90\\/10\\/1 CH2Cl2\\/MeOH\\/NH4OH) to give the title compound as an off-white solid (0.17 g, 21%). MS (ES+) 275.1\",\"reactant_000\":\"ClCCCN1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"O=C1NCCc2ccc(O)cc21\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9936749935150146,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCc2ccc(OCCCN3CCCC3)cc21\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.Cl[CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1>CN(C=O)C>[N:17]1([CH2:16][CH2:15][CH2:14][O:1][C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][NH:8][C:9]3=[O:12])=[CH:4][CH:3]=2)[CH2:21][CH2:20][CH2:19][CH2:18]1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"O\",\"distance\":0.0064890384674072266,\"rxn_id\":\"ord-a4995629b6204d468d5b4336e14f9897\",\"index\":449830,\"rxn_smiles\":\"CC(C)O.COc1cc2oc(=O)c(C)c(C)c2cc1O.Cl.ClCCCN1CCN(Cc2ccc(Cl)cc2)CC1.O>>COc1cc2oc(=O)c(C)c(C)c2cc1OCCCN1CCN(Cc2ccc(Cl)cc2)CC1\",\"procedure_details\":\"Method D (5 h at 90° C.); starting materials: 6-hydroxy-7-methoxy-3,4-dimethyl-2H-1-benzopyran-2-one (example 103) and 1-[(4-chlorophenyl)methyl]-4-(3-chloropropyl)piperazine; yield: 74%; fusion point 96°-97° C. (from isopropanol and petroleum ether). Hydrochloride (x 2 HCl): method G; yield 95%; fusion point 255°-260° C. (from isopropanol and water).\",\"reactant_000\":\"COc1cc2oc(=O)c(C)c(C)c2cc1O\",\"reactant_002\":null,\"reactant_001\":\"ClCCCN1CCN(Cc2ccc(Cl)cc2)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9935109615325928,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2oc(=O)c(C)c(C)c2cc1OCCCN1CCN(Cc2ccc(Cl)cc2)CC1\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([O:15][CH3:16])=[CH:4][C:5]2[O:10][C:9](=[O:11])[C:8]([CH3:12])=[C:7]([CH3:13])[C:6]=2[CH:14]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:25]2[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][CH2:33]Cl)[CH2:27][CH2:26]2)=[CH:20][CH:19]=1.C(O)(C)C.Cl>O>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:24][N:25]2[CH2:26][CH2:27][N:28]([CH2:31][CH2:32][CH2:33][O:1][C:2]3[C:3]([O:15][CH3:16])=[CH:4][C:5]4[O:10][C:9](=[O:11])[C:8]([CH3:12])=[C:7]([CH3:13])[C:6]=4[CH:14]=3)[CH2:29][CH2:30]2)=[CH:22][CH:23]=1\",\"yield_000\":74.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.006968259811401367,\"rxn_id\":\"ord-f52c27df0db34e649570e622c832e52b\",\"index\":481109,\"rxn_smiles\":\"CC(C)O.Cl.ClCCCN1CCOCC1.O=c1oc2ccccc2c(O)c1-c1ccccc1>>O=c1oc2ccccc2c(OCCCN2CCOCC2)c1-c1ccccc1\",\"procedure_details\":\"This compound is obtained by the method indicated in Example 8, from 14.3 g. (0.06 mol) of 4-hydroxy-3-phenyl-coumarin and 15.6 g. (0.078 mol) of 3-morpholino-1-chloropropane hydrochloride. 15.6 g. of a white solid are isolated. Yield 71% (theoretical yield 21.9 g.); M.P. 82° C. (isopropanol).\",\"reactant_000\":\"O=c1oc2ccccc2c(O)c1-c1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCN1CCOCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9930317401885986,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=c1oc2ccccc2c(OCCCN2CCOCC2)c1-c1ccccc1\",\"rxn_str\":\"[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][C:4](=[O:12])[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl.[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28]Cl)[CH2:22][CH2:21]1>C(O)(C)C>[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][O:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[O:5][C:4](=[O:12])[C:3]=2[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:22][CH2:21]1\",\"yield_000\":71.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.007157027721405029,\"rxn_id\":\"ord-52e5908a3e544508ac862e3188228f8e\",\"index\":355561,\"rxn_smiles\":\"ClCCCN1CCCC1.N#CCc1ccccc1O>>N#CCc1ccccc1OCCCN1CCCC1\",\"procedure_details\":\"The title compound was prepared from 2-hydroxy-benzeneacetonitrile (J. Org. Chem.; 66, 3435; 2001) and 1-(3-chloropropyl)pyrrolidine, using a method similar to that of preparation 104, as a pale brown gum in 58% yield. 1H NMR (400 MHz, CD3OD) δ: 7.33-7.25 (2H, m), 7.02-6.90 (2H, m), 4.12-4.09 (2H, m), 3.75 (2H, s), 2.76-2.72 (2H, m), 2.62-2.57 (4H, m), 2.09-2.02 (2H, m), 1.87-1.78 (4H, m); LRMS APCI m\\/z 245 [M+H]+\",\"reactant_000\":\"ClCCCN1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"N#CCc1ccccc1O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992842972278595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#CCc1ccccc1OCCCN1CCCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]#[N:10].Cl[CH2:12][CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1>>[N:15]1([CH2:14][CH2:13][CH2:12][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:8][C:9]#[N:10])[CH2:19][CH2:18][CH2:17][CH2:16]1\",\"yield_000\":58.0}]","literatureScore":0.99,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002769649028778076,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9972303509712219,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0031270384788513184,\"rxn_id\":\"ord-dcc1a5efa86d4d09b08ec14f86ec1748\",\"index\":264188,\"rxn_smiles\":\"Cl.O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12>>Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"procedure_details\":\"A solution of stannous chloride dihydrate (3.7 g, 16 mmol) in 10 ml of conc. hydrochloric acid was added dropwise to a stirred suspension of 2,3-dihydroxy-6-nitrobenzo(f)quinoxaline (1.3 g, 5 mmol) in 8 ml of conc. hydrochloric acid. Then the mixture was stirred at 60-70° C. on an oil bath for 2 h. After cooling on ice, the precipitate was collected, dissolved in boiling water (1 1), filtered while hot, and neutralized to pH 6 with solid sodium hydrogen carbonate. The yellow product was isolated and recrystallized from DMF\\/water, washed with water, ethanol and ether and finally dried at 110 ° C. to give 0.90 g (63%) of pure title compound, m.p. >300° C., IR (KBr): 1690, ? 1640 and 1605 cm-1,1H-NMR (DMSO-d6): 5.8 (broad s, 2H,NH2), 6.63(s,1H, H-5), 7.2-8.7 (m, 4H, ArH), 11.8 (broad s, 2H, 20H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968729615211487,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([OH:19])=[N:4][C:5]2[CH:6]=[C:7]([N+:16]([O-])=O)[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[N:11]=1>Cl>[NH2:16][C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]2[N:11]=[C:2]([OH:1])[C:3]([OH:19])=[N:4][C:5]=2[CH:6]=1\",\"yield_000\":79.2},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.00328141450881958,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9967185854911804,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003656148910522461,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963438510894775,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003899812698364258,\"rxn_id\":\"ord-fc93af0f0d9a40e284c2500298acaf93\",\"index\":573049,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"The crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine was dissolved in THF and reduced using Raney nickel catalyst to yield N4-(3-Chloro-4-fluoro-phenyl)-7-(2,2-difluoro-ethoxy)-quinazoline-4,6-diamine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961001873016357,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C1COCC1.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null}]","literatureScore":1,"label":"UA CF T5 AT ER TTL ALL>>33","id":33},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":283}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":283}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":283}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":283}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.68,"id":154,"pathId":283}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEFNIUDZICAGOU","smiles":"NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1O","intrinsicScore":0.051,"id":33,"pathId":283}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[N+:21](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[NH2:21])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"AT T5 ER UA TTL ALL>>13","id":13},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"PIAZYBLGBSMNLX","smiles":"ClCCCN1CCOCC1","intrinsicScore":0.051,"id":13,"pathId":283}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":283}],"RXN":"[cH:4]1[cH:3][c:2]([c:1]([cH:6][c:5]1[NH:7][c:8]2[c:9]3[cH:19][c:17]([c:15]([cH:14][c:10]3[n:11][cH:12][n:13]2)[OH:16])[NH2:18])[Cl:21])[F:20].[CH2:22]1[CH2:27][O:26][CH2:25][CH2:24][N:23]1[CH2:28][CH2:29][CH2:30]Cl>>[cH:4]1[cH:3][c:2]([c:1]([cH:6][c:5]1[NH:7][c:8]2[c:9]3[cH:19][c:17]([c:15]([cH:14][c:10]3[n:11][cH:12][n:13]2)[O:16][CH2:30][CH2:29][CH2:28][N:23]4[CH2:22][CH2:27][O:26][CH2:25][CH2:24]4)[NH2:18])[Cl:21])[F:20];1.7.9;Williamson"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":283}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":283}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.144","depth":0,"reaction":{"label":">>0","id":0,"pathId":694},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":694}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":694}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":694}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":694}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":694}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":694}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":694}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":694}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":694}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":694}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":694}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-7.172","depth":0,"reaction":{"label":">>0","id":0,"pathId":29},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004968404769897461,\"rxn_id\":\"ord-67cd89c92ec043eaa8c192a52c6055e1\",\"index\":71209,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)c(F)c2)cc1>>N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"procedure_details\":\"The product from Example 167A and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (99% yield). 1HNMR (300 MHz, CDCl3) δ2.30 (m, 2H), 3.80 (m, 2H), 4.25 (m, 2H), 7.12-7.75 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)c(F)c2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950315952301025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)=[CH:3][C:2]=1[F:1]\",\"yield_000\":99.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005435526371002197,\"rxn_id\":\"ord-593d5907c892416383020940bf139801\",\"index\":592545,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)cc2)cc1F>>N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"procedure_details\":\"The product from Example 166B and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (98% yield). 1HNMR (300 MHz, CDCl3) δ2.25 (m, 2H), 3.80 (m, 2H), 4.20 (m, 2H), 7.00-7.65 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)cc2)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945644736289978,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([F:1])[CH:3]=2)=[CH:11][CH:12]=1\",\"yield_000\":98.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005583524703979492,\"rxn_id\":\"ord-f2089ee29c9c49d6bda509b96fde9e15\",\"index\":355059,\"rxn_smiles\":\"ClCCCBr.Cn1ncc(-c2ccc(O)cc2)cc1=O>>Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"procedure_details\":\"5-[4-(3-Chloro-propoxy)-phenyl]-2-methyl-2H-pyridazin-3-one was prepared from 5-(4-hydroxy-phenyl)-2-methyl-2H-pyridazin-3-one with 1-bromo-3-chloro-propane using the procedure described in Example 86 Step 3; Mp 90-91° C.; MS m\\/z 279 (M+H).\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"Cn1ncc(-c2ccc(O)cc2)cc1=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944164752960205,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0058318376541137695,\"rxn_id\":\"ord-0943760d2d71451cb76c1188d0d02866\",\"index\":410217,\"rxn_smiles\":\"ClCCCBr.O=C1NCCn2c1cc1cc(O)cnc12>>O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"procedure_details\":\"The title compound was synthesized in analogy to example 2, intermediate, from 7-hydroxy-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one (example 84, intermediate a) and 1-bromo-3-chloropropane, to give the desired product as a light yellow solid (80%).\",\"reactant_000\":\"O=C1NCCn2c1cc1cc(O)cnc12\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941681623458862,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"rxn_str\":\"[OH:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1\",\"yield_000\":80.0},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.006563842296600342,\"rxn_id\":\"ord-cbbf3a06c7d04efaab9b011975b2bcaf\",\"index\":118810,\"rxn_smiles\":\"CC(C)=O.ClCCCBr.O=C1CSc2cc(O)ccc2N1>>O=C1CSc2cc(OCCCCl)ccc2N1\",\"procedure_details\":\"After a mixture consisting of 7-hydroxy-3,4-dihydro-2H-1,4-benzothiazin-3-one (1.812 g, 10 mmol), 1bromo-3-chloropropane (2.362 g, 15 mmol), potassium carbate (4.146 g, 30 mmol) and acetone (40 mmol) was heated under reflux and stirring for 24 hours, insolube matter was filtered off, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel column (developer: chloroform) to purify the same, and was then recrystallized from acetone. The title compound (1.300 g) was obtained as yellow leaflets (yield: 50.4%).\",\"reactant_000\":\"O=C1CSc2cc(O)ccc2N1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9934361577033997,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CSc2cc(OCCCCl)ccc2N1\",\"rxn_str\":\"[OH:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.Br[CH2:14][CH2:15][CH2:16][Cl:17].CC(C)=O>>[Cl:17][CH2:16][CH2:15][CH2:14][O:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1\",\"yield_000\":50.4}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":29}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":29}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":29}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":29}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.43,"id":154,"pathId":29}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":4,"reaction":{"label":"TTL ALL T5 UA ER ALL>>90","id":90},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MFESCIUQSIBMSM","smiles":"ClCCCBr","intrinsicScore":0.43,"id":90,"pathId":29}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":29}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:26]([CH2:25][Cl:24])[CH2:27]Br>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:23][CH2:27][CH2:26][CH2:25][Cl:24])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.9;Williamson"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":29}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":29}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":29}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":29}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":29}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.185","depth":0,"reaction":{"label":">>0","id":0,"pathId":2066},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.002469778060913086,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9975302219390869,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.002480626106262207,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9975193738937378,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(C(C)C)C(C)C\",\"distance\":0.0029109716415405273,\"rxn_id\":\"ord-fbc6602e838844ea8049e8f1cc4695df\",\"index\":724691,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"procedure_details\":\"Diisopropylethylamine (0.09 ml, 0.5 mmol) was added in one portion to a stirred solution of 4-amino-N-(2-morpholin-4-yl-ethyl)-benzenesulfonamide (0.1 g, 0.35 mmol) in THF (3 ml) at room temperature. To this mixture was added acryloyl chloride (0.03 ml, 0.38 mmol) in one portion and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After this time, the mixture was concentrated under vacuum and the resulting residue purified by Prep HPLC to give the title compound (6 mg, 5% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9970890283584595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_str\":\"C(N(C(C)C)CC)(C)C.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[N:23]1([CH2:22][CH2:21][NH:20][S:17]([C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:16][CH:15]=2)(=[O:19])=[O:18])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1\",\"yield_000\":5.1},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0030384063720703125,\"rxn_id\":\"ord-3e531f95b682495d934d2f5fe24064c6\",\"index\":208714,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"procedure_details\":\"4-(4-Amino-benzenesulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.25 g, 0.67 mmol) was dissolved in THF (10 ml). To this was added diisopropylethylamine (0.33 ml, 1.9 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.06 ml, 0.74 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material was purified by column chromatography (elution: 20% heptane, 80% ethyl acetate) to give the title compound (57 mg, 20% yield) as a white powder.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9969615936279297,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:36](=[O:39])[CH:37]=[CH2:38])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":19.8},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.003479301929473877,\"rxn_id\":\"ord-2a9510bf8eea48eb89d49af6327453f4\",\"index\":594742,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"procedure_details\":\"4-(4-Amino-2-trifluoromethyl-benzensulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.44 g, 0.11 mmol) was dissolved in THF (15 ml). To this solution was added diisopropylethylamine (0.52 ml, 0.33 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.09 ml, 0.11 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material, was purified by preparative HPLC to give the title compound (70 mg, 14% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9965206980705261,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=2[C:27]([F:30])([F:29])[F:28])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:40](=[O:43])[CH:41]=[CH2:42])=[CH:22][C:21]=2[C:27]([F:30])([F:28])[F:29])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":127.9}]","literatureScore":1,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":2066}]},{"depth":7,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":2066}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":2066}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":2066}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2066}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2066}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":2066}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":2066}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":2066}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.62,"id":37,"pathId":2066}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.62,"id":7,"pathId":2066}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2066}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:22]1[cH:23][c:24]([c:25]([cH:27][c:21]1[NH:20][c:19]2[c:18]3[cH:33][c:34]([c:15]([cH:16][c:17]3[n+:31]([cH:30][n:29]2)[O-:32])[O:14][CH2:13][CH2:12][CH2:11][N:10]4[CH2:5][CH2:6][O:7][CH2:8][CH2:9]4)[NH2:35])[Cl:26])[F:28]>C1CCOC1.C(N(CC)C(C)C)(C)C>[CH2:4]=[CH:3][C:1](=[O:2])[NH:35][c:34]1[cH:33][c:18]2[c:17]([cH:16][c:15]1[O:14][CH2:13][CH2:12][CH2:11][N:10]3[CH2:5][CH2:6][O:7][CH2:8][CH2:9]3)[n+:31]([cH:30][n:29][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:25]([cH:27]4)[Cl:26])[F:28])[O-:32];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2066}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-7.212","depth":0,"reaction":{"label":">>0","id":0,"pathId":9},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0029944181442260742,\"rxn_id\":\"ord-e0b0f01cfc8846efa4465e6a5288872d\",\"index\":23488,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (1.5 g, 2.96 mmol), 4-(3-hydroxypropyl)morpholine (0.623 mL, 4.5 mmol), triphenylphosphine (1.18 g, 4.5 mmol), and dichloromethane (50 mL) was added diisopropyl azodicarboxylate (0.886 mL, 4.5 mmol). The mixture was stirred at room temperature for 16 h, monitored by LCMS. After removal of solvent, the crude mixture was separated by flash column chromatography (silica), eluting with 5% methanol in dichloromethane to give N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N\\u2032-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (890 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.36 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.83 (m, 1H), 7.64 (m, 2H), 7.57 (s, 1H), 7.44 (m, 3H), 7.18 (t, 2H), 4.27 (m, 2H), 3.99 (s, 3H), 3.61 (m, 6H), 2.40 (m, 4H), 2.01 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.3.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9970055818557739,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:37][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:36][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1\",\"yield_000\":47.5},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CCOCC\",\"distance\":0.003035128116607666,\"rxn_id\":\"ord-fab5133cf99a4d628c51ef65011713b7\",\"index\":182883,\"rxn_smiles\":\"CCCCP(CCCC)CCCC.CCOCC.COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O.ClCCl.O=C(N=NC(=O)N1CCCCC1)N1CCCCC1.OCCN1CCSCC1>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"procedure_details\":\"4-(2-Hydroxyethyl)thiomorpholine (114 mg, 0.78 mmol), (J. Am. Chem. Soc. 1934. 56, 1720), in methylene chloride (1 ml) followed by 1,1\\u2032-(azodicarbonyl)dipiperidine (525 mg. 2.08 mmol) were added to a stirred solution of 4-(4-chloro-2-fluoroanilino)7-hydroxy-6 methoxyquinazoline (225 mg, 0.70 mmol), (prepared as described for the starting material in Example 2), and tributylphosphine (0.51 ml, 2.08 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours and allowed to stand for a further 18 hours. Ether (8 ml) was added, the precipitate removed by filtration and the solvent removed from the filtrate by evaporation. The residue was dissolved in acetone and ethereal hydrogen chloride (2.5 m! of a 1M solution) added. The precipitated product was collected by filtration and purified by column chromatography eluting with methylene chloride\\/methanol\\/aqueous ammonia (150\\/8\\/1). The purified product was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazoline (70 mg, 22%) as a pale yellow solid.\",\"reactant_000\":\"OCCN1CCSCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O\",\"rxn_time\":3.5,\"reactant_003\":null,\"similarity\":0.9969648718833923,\"agent_000\":\"CCCCP(CCCC)CCCC\",\"agent_001\":\"O=C(N=NC(=O)N1CCCCC1)N1CCCCC1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][S:7][CH2:6][CH2:5]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40](O)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([O:1][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][S:7][CH2:6][CH2:5]4)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1\",\"yield_000\":22.3},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0032836198806762695,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9967163801193237,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0037235617637634277,\"rxn_id\":\"ord-ae2e2a15cfb44e3c8c0bddafaf4489b5\",\"index\":501292,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O.OCCc1ccncc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"procedure_details\":\"To a solution of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea (0.1 g, 0.24 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and triphenylphosphine (0.0944 g, 0.36 mmol) in 10 mL of dry THF was added diisopropylazo-dicarboxylate (0.0728 g, 0.36 mmol) at ambient temperature. The mixture was stirred for 2 hours. Next, additional triphenylphosphine (0.0944 g, 0.36 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and diisopropylazodicarboxylate were added and the reaction mixture further stirred at room temperature overnight. The solvent from the reaction mixture was evaporated and the crude residue was dissolved in 5.0 mL of DMSO and purified by RP-HPLC. The proper fractions were collected and concentrated to ¼ volume. The aqueous solution was neutralized with 1N NaOH and extracted with ethyl acetate (2×, 59 mL). The organic layer was dried with sodium sulfate, filtered and evaporated to dryness to afford 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyridin-4-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea as a brown solid in 44% yield. LCMS m\\/z (%)=526 (M+H 79Br, 100), 528 (M+H 81Br, 67). 1H NMR (DMSO-d6) δ: 9.33 (bs, 1H), 9.24 (bs, 1H), 8.39 (dd, J=4.44 and 1.48 Hz, 2H), 7.63 (d, J=7.28 Hz, 1H), 7.59 (s, 1H), 7.56 (dd, J=8.94 and 2.71 Hz, 2H), 7.48 (m, 1H), 7.34 (d, J=2.67, 1H), 7.31 (d, J=2.67, 1H), 7.28 (dd, J=6.88 and 4.87 Hz, 2H), 7.14 (d, J=9.05 Hz, 1H), 7.09 (d, J=5.93 Hz, 1H), 4.01-4.2 (m, 2H), 3.48 (s, 3H), 2.96-2.91 (m, 2H).\",\"reactant_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCc1ccncc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9962764382362366,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"rxn_str\":\"[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[OH:14].O[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[O:14][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1\",\"yield_000\":44.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0038225650787353516,\"rxn_id\":\"ord-33bfcf35bf734b52b59d70aa5d195f4f\",\"index\":462262,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Diethyl azodicarboxylate (2.67 ml, 17 mmol) was added dropwise to a solution of 3-morpholinopropan-1-ol (1.54 g, 10 mmol), 7-hydroxy-3,4-dihydro-6-methoxy-3-((pivaloyloxy)methyl)quinazolin-4-one (2.6 g, 8.5 mmol) and triphenylphosphine (4.45 g, 17 mmol) in methylene chloride (40 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride\\/methanol (97\\/3 followed by 95\\/5) to give 3,4-dihydro-6-methoxy-3-((pivaloyloxy)metyl)-7-(3-morpholinopropoxy)quinazolin-4-one (3.6 g, 97%).\",\"reactant_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961774349212646,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]1.O[C:24]1[CH:33]=[C:32]2[C:27]([C:28](=[O:42])[N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[N:31]2)=[CH:26][C:25]=1[O:43][CH3:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:44][O:43][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:24]=1[O:22][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[N:31]=[CH:30][N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]2=[O:42]\",\"yield_000\":97.7}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":9}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":9}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":9}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":9}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":9}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":4,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":9}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.42,"id":154,"pathId":9}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":9}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":9}],"RXN":"[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[OH:17])[N+:19](=[O:21])[O-:20])[Cl:3])[F:5].[CH2:25]1[CH2:26][O:27][CH2:28][CH2:29][N:24]1[CH2:30][CH2:31][CH2:32]O>C(C)CCP(CCCC)CCCC.ClCCl.C1CN(CCC1)C(N=NC(N2CCCCC2)=O)=O>[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:32][CH2:31][CH2:30][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[N+:19](=[O:21])[O-:20])[Cl:3])[F:5];1.7.7;Mitsunobu"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":9}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":9}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":9}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.228","depth":0,"reaction":{"label":">>0","id":0,"pathId":2073},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.002469778060913086,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9975302219390869,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.002480626106262207,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9975193738937378,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(C(C)C)C(C)C\",\"distance\":0.0029109716415405273,\"rxn_id\":\"ord-fbc6602e838844ea8049e8f1cc4695df\",\"index\":724691,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"procedure_details\":\"Diisopropylethylamine (0.09 ml, 0.5 mmol) was added in one portion to a stirred solution of 4-amino-N-(2-morpholin-4-yl-ethyl)-benzenesulfonamide (0.1 g, 0.35 mmol) in THF (3 ml) at room temperature. To this mixture was added acryloyl chloride (0.03 ml, 0.38 mmol) in one portion and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After this time, the mixture was concentrated under vacuum and the resulting residue purified by Prep HPLC to give the title compound (6 mg, 5% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9970890283584595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_str\":\"C(N(C(C)C)CC)(C)C.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[N:23]1([CH2:22][CH2:21][NH:20][S:17]([C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:16][CH:15]=2)(=[O:19])=[O:18])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1\",\"yield_000\":5.1},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0030384063720703125,\"rxn_id\":\"ord-3e531f95b682495d934d2f5fe24064c6\",\"index\":208714,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"procedure_details\":\"4-(4-Amino-benzenesulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.25 g, 0.67 mmol) was dissolved in THF (10 ml). To this was added diisopropylethylamine (0.33 ml, 1.9 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.06 ml, 0.74 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material was purified by column chromatography (elution: 20% heptane, 80% ethyl acetate) to give the title compound (57 mg, 20% yield) as a white powder.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9969615936279297,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:36](=[O:39])[CH:37]=[CH2:38])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":19.8},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.003479301929473877,\"rxn_id\":\"ord-2a9510bf8eea48eb89d49af6327453f4\",\"index\":594742,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"procedure_details\":\"4-(4-Amino-2-trifluoromethyl-benzensulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.44 g, 0.11 mmol) was dissolved in THF (15 ml). To this solution was added diisopropylethylamine (0.52 ml, 0.33 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.09 ml, 0.11 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material, was purified by preparative HPLC to give the title compound (70 mg, 14% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9965206980705261,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=2[C:27]([F:30])([F:29])[F:28])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:40](=[O:43])[CH:41]=[CH2:42])=[CH:22][C:21]=2[C:27]([F:30])([F:28])[F:29])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":127.9}]","literatureScore":1,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004677474498748779,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9953225255012512,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.004711925983428955,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.995288074016571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004857063293457031,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.995142936706543,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.0048857927322387695,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9951142072677612,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":\"O\",\"distance\":0.005634188652038574,\"rxn_id\":\"ord-d91c98b6083b42d28e154dc79ab3de41\",\"index\":515521,\"rxn_smiles\":\"C1COCCN1.Cc1ccccc1.Nc1ccc(C(=O)OCCCCl)c(N)c1.O>>Nc1ccc(C(=O)OCCCN2CCOCC2)c(N)c1\",\"procedure_details\":\"A mixture of 35 ml of toluene, 4.6 g of (3-chloropropyl)-2,4-diaminobenzoate and 3.5 g of morpholine was refluxed for 10 hrs, cooled to room temperature, and poured into 70 ml of water with stirring. The precipitate was filtered, washed with hexane and dried. Recrystallization from toluene gave 2.6 g (3-morpholinopropyl)-2,4-diaminobenzoate, a white solid, mp 96° C.\",\"reactant_000\":\"Nc1ccc(C(=O)OCCCCl)c(N)c1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9943658113479614,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C(=O)OCCCN2CCOCC2)c(N)c1\",\"rxn_str\":\"C1(C)C=CC=CC=1.Cl[CH2:9][CH2:10][CH2:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=1[NH2:21].[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>O>[O:26]1[CH2:27][CH2:28][N:23]([CH2:9][CH2:10][CH2:11][O:12][C:13](=[O:22])[C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=2[NH2:21])[CH2:24][CH2:25]1\",\"yield_000\":46.3}]","literatureScore":1,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.014116823673248291,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9858831763267517,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.016109049320220947,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.983890950679779,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01629471778869629,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9837052822113037,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.017170846462249756,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9828291535377502,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.018261253833770752,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9817387461662292,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"AT ER UA TTL ALL>>173","id":173},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":2073}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":2073}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2073}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2073}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":2073}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":2073}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":486,"pathId":2073}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YAIVOKCSYDYBSV","smiles":"NC1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.098,"id":173,"pathId":2073}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[N+:8](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[NH2:8])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":2073}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.62,"id":37,"pathId":2073}],"RXN":"[cH:24]1[cH:25][c:26]([c:28]([cH:29][c:23]1[NH:22][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n+:18]([cH:17][n:16]2)[O-:21])[O:10][CH2:9][CH2:8][CH2:7]Cl)[NH2:31])[Cl:30])[F:27].[CH2:3]1[CH2:2][O:1][CH2:6][CH2:5][NH:4]1>C(CCC)CC.O=C(C)OCC.COCCOC>[cH:24]1[cH:25][c:26]([c:28]([cH:29][c:23]1[NH:22][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n+:18]([cH:17][n:16]2)[O-:21])[O:10][CH2:9][CH2:8][CH2:7][N:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)[NH2:31])[Cl:30])[F:27];1.6.4;Chloro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.62,"id":7,"pathId":2073}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2073}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:22]1[cH:23][c:24]([c:25]([cH:27][c:21]1[NH:20][c:19]2[c:18]3[cH:33][c:34]([c:15]([cH:16][c:17]3[n+:31]([cH:30][n:29]2)[O-:32])[O:14][CH2:13][CH2:12][CH2:11][N:10]4[CH2:5][CH2:6][O:7][CH2:8][CH2:9]4)[NH2:35])[Cl:26])[F:28]>C1CCOC1.C(N(CC)C(C)C)(C)C>[CH2:4]=[CH:3][C:1](=[O:2])[NH:35][c:34]1[cH:33][c:18]2[c:17]([cH:16][c:15]1[O:14][CH2:13][CH2:12][CH2:11][N:10]3[CH2:5][CH2:6][O:7][CH2:8][CH2:9]3)[n+:31]([cH:30][n:29][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:25]([cH:27]4)[Cl:26])[F:28])[O-:32];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2073}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-7.262","depth":0,"reaction":{"label":">>0","id":0,"pathId":2060},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.002469778060913086,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9975302219390869,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.002480626106262207,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9975193738937378,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(C(C)C)C(C)C\",\"distance\":0.0029109716415405273,\"rxn_id\":\"ord-fbc6602e838844ea8049e8f1cc4695df\",\"index\":724691,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"procedure_details\":\"Diisopropylethylamine (0.09 ml, 0.5 mmol) was added in one portion to a stirred solution of 4-amino-N-(2-morpholin-4-yl-ethyl)-benzenesulfonamide (0.1 g, 0.35 mmol) in THF (3 ml) at room temperature. To this mixture was added acryloyl chloride (0.03 ml, 0.38 mmol) in one portion and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After this time, the mixture was concentrated under vacuum and the resulting residue purified by Prep HPLC to give the title compound (6 mg, 5% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9970890283584595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_str\":\"C(N(C(C)C)CC)(C)C.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[N:23]1([CH2:22][CH2:21][NH:20][S:17]([C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:16][CH:15]=2)(=[O:19])=[O:18])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1\",\"yield_000\":5.1},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0030384063720703125,\"rxn_id\":\"ord-3e531f95b682495d934d2f5fe24064c6\",\"index\":208714,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"procedure_details\":\"4-(4-Amino-benzenesulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.25 g, 0.67 mmol) was dissolved in THF (10 ml). To this was added diisopropylethylamine (0.33 ml, 1.9 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.06 ml, 0.74 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material was purified by column chromatography (elution: 20% heptane, 80% ethyl acetate) to give the title compound (57 mg, 20% yield) as a white powder.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9969615936279297,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:36](=[O:39])[CH:37]=[CH2:38])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":19.8},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.003479301929473877,\"rxn_id\":\"ord-2a9510bf8eea48eb89d49af6327453f4\",\"index\":594742,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"procedure_details\":\"4-(4-Amino-2-trifluoromethyl-benzensulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.44 g, 0.11 mmol) was dissolved in THF (15 ml). To this solution was added diisopropylethylamine (0.52 ml, 0.33 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.09 ml, 0.11 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material, was purified by preparative HPLC to give the title compound (70 mg, 14% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9965206980705261,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=2[C:27]([F:30])([F:29])[F:28])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:40](=[O:43])[CH:41]=[CH2:42])=[CH:22][C:21]=2[C:27]([F:30])([F:28])[F:29])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":127.9}]","literatureScore":1,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0026927590370178223,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9973072409629822,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.002873241901397705,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9971267580986023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0033760666847229004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9966239333152771,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003621220588684082,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9963787794113159,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003737330436706543,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9962626695632935,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":2060}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":2060}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2060}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2060}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":2060}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":2060}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.095,"id":486,"pathId":2060}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.095,"id":9,"pathId":2060}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":2060}],"RXN":"[cH:21]1[cH:22][c:23]([c:25]([cH:26][c:20]1[NH:19][c:18]2[c:2]3[cH:1][c:6]([c:5]([cH:4][c:3]3[n+:14]([cH:16][n:17]2)[O-:15])[O:10][CH2:11][CH2:12][CH2:13]Cl)[N+:7](=[O:8])[O-:9])[Cl:27])[F:24].[CH2:30]1[CH2:29][O:28][CH2:33][CH2:32][NH:31]1>>[cH:21]1[cH:22][c:23]([c:25]([cH:26][c:20]1[NH:19][c:18]2[c:2]3[cH:1][c:6]([c:5]([cH:4][c:3]3[n+:14]([cH:16][n:17]2)[O-:15])[O:10][CH2:11][CH2:12][CH2:13][N:31]4[CH2:30][CH2:29][O:28][CH2:33][CH2:32]4)[N+:7](=[O:8])[O-:9])[Cl:27])[F:24];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.62,"id":37,"pathId":2060}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.62,"id":7,"pathId":2060}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2060}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:22]1[cH:23][c:24]([c:25]([cH:27][c:21]1[NH:20][c:19]2[c:18]3[cH:33][c:34]([c:15]([cH:16][c:17]3[n+:31]([cH:30][n:29]2)[O-:32])[O:14][CH2:13][CH2:12][CH2:11][N:10]4[CH2:5][CH2:6][O:7][CH2:8][CH2:9]4)[NH2:35])[Cl:26])[F:28]>C1CCOC1.C(N(CC)C(C)C)(C)C>[CH2:4]=[CH:3][C:1](=[O:2])[NH:35][c:34]1[cH:33][c:18]2[c:17]([cH:16][c:15]1[O:14][CH2:13][CH2:12][CH2:11][N:10]3[CH2:5][CH2:6][O:7][CH2:8][CH2:9]3)[n+:31]([cH:30][n:29][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:25]([cH:27]4)[Cl:26])[F:28])[O-:32];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2060}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-7.293","depth":0,"reaction":{"label":">>0","id":0,"pathId":2069},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.002469778060913086,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9975302219390869,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.002480626106262207,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9975193738937378,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(C(C)C)C(C)C\",\"distance\":0.0029109716415405273,\"rxn_id\":\"ord-fbc6602e838844ea8049e8f1cc4695df\",\"index\":724691,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"procedure_details\":\"Diisopropylethylamine (0.09 ml, 0.5 mmol) was added in one portion to a stirred solution of 4-amino-N-(2-morpholin-4-yl-ethyl)-benzenesulfonamide (0.1 g, 0.35 mmol) in THF (3 ml) at room temperature. To this mixture was added acryloyl chloride (0.03 ml, 0.38 mmol) in one portion and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After this time, the mixture was concentrated under vacuum and the resulting residue purified by Prep HPLC to give the title compound (6 mg, 5% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9970890283584595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_str\":\"C(N(C(C)C)CC)(C)C.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[N:23]1([CH2:22][CH2:21][NH:20][S:17]([C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:16][CH:15]=2)(=[O:19])=[O:18])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1\",\"yield_000\":5.1},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0030384063720703125,\"rxn_id\":\"ord-3e531f95b682495d934d2f5fe24064c6\",\"index\":208714,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"procedure_details\":\"4-(4-Amino-benzenesulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.25 g, 0.67 mmol) was dissolved in THF (10 ml). To this was added diisopropylethylamine (0.33 ml, 1.9 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.06 ml, 0.74 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material was purified by column chromatography (elution: 20% heptane, 80% ethyl acetate) to give the title compound (57 mg, 20% yield) as a white powder.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9969615936279297,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:36](=[O:39])[CH:37]=[CH2:38])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":19.8},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.003479301929473877,\"rxn_id\":\"ord-2a9510bf8eea48eb89d49af6327453f4\",\"index\":594742,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"procedure_details\":\"4-(4-Amino-2-trifluoromethyl-benzensulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.44 g, 0.11 mmol) was dissolved in THF (15 ml). To this solution was added diisopropylethylamine (0.52 ml, 0.33 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.09 ml, 0.11 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material, was purified by preparative HPLC to give the title compound (70 mg, 14% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9965206980705261,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=2[C:27]([F:30])([F:29])[F:28])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:40](=[O:43])[CH:41]=[CH2:42])=[CH:22][C:21]=2[C:27]([F:30])([F:28])[F:29])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":127.9}]","literatureScore":1,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":2069}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":2069}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":2069}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":2069}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2069}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2069}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":2069}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":2069}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":2069}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.62,"id":37,"pathId":2069}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.62,"id":7,"pathId":2069}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2069}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:22]1[cH:23][c:24]([c:25]([cH:27][c:21]1[NH:20][c:19]2[c:18]3[cH:33][c:34]([c:15]([cH:16][c:17]3[n+:31]([cH:30][n:29]2)[O-:32])[O:14][CH2:13][CH2:12][CH2:11][N:10]4[CH2:5][CH2:6][O:7][CH2:8][CH2:9]4)[NH2:35])[Cl:26])[F:28]>C1CCOC1.C(N(CC)C(C)C)(C)C>[CH2:4]=[CH:3][C:1](=[O:2])[NH:35][c:34]1[cH:33][c:18]2[c:17]([cH:16][c:15]1[O:14][CH2:13][CH2:12][CH2:11][N:10]3[CH2:5][CH2:6][O:7][CH2:8][CH2:9]3)[n+:31]([cH:30][n:29][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:25]([cH:27]4)[Cl:26])[F:28])[O-:32];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2069}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-7.32","depth":0,"reaction":{"label":">>0","id":0,"pathId":12},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0029944181442260742,\"rxn_id\":\"ord-e0b0f01cfc8846efa4465e6a5288872d\",\"index\":23488,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (1.5 g, 2.96 mmol), 4-(3-hydroxypropyl)morpholine (0.623 mL, 4.5 mmol), triphenylphosphine (1.18 g, 4.5 mmol), and dichloromethane (50 mL) was added diisopropyl azodicarboxylate (0.886 mL, 4.5 mmol). The mixture was stirred at room temperature for 16 h, monitored by LCMS. After removal of solvent, the crude mixture was separated by flash column chromatography (silica), eluting with 5% methanol in dichloromethane to give N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N\\u2032-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (890 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.36 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.83 (m, 1H), 7.64 (m, 2H), 7.57 (s, 1H), 7.44 (m, 3H), 7.18 (t, 2H), 4.27 (m, 2H), 3.99 (s, 3H), 3.61 (m, 6H), 2.40 (m, 4H), 2.01 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.3.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9970055818557739,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:37][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:36][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1\",\"yield_000\":47.5},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CCOCC\",\"distance\":0.003035128116607666,\"rxn_id\":\"ord-fab5133cf99a4d628c51ef65011713b7\",\"index\":182883,\"rxn_smiles\":\"CCCCP(CCCC)CCCC.CCOCC.COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O.ClCCl.O=C(N=NC(=O)N1CCCCC1)N1CCCCC1.OCCN1CCSCC1>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"procedure_details\":\"4-(2-Hydroxyethyl)thiomorpholine (114 mg, 0.78 mmol), (J. Am. Chem. Soc. 1934. 56, 1720), in methylene chloride (1 ml) followed by 1,1\\u2032-(azodicarbonyl)dipiperidine (525 mg. 2.08 mmol) were added to a stirred solution of 4-(4-chloro-2-fluoroanilino)7-hydroxy-6 methoxyquinazoline (225 mg, 0.70 mmol), (prepared as described for the starting material in Example 2), and tributylphosphine (0.51 ml, 2.08 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours and allowed to stand for a further 18 hours. Ether (8 ml) was added, the precipitate removed by filtration and the solvent removed from the filtrate by evaporation. The residue was dissolved in acetone and ethereal hydrogen chloride (2.5 m! of a 1M solution) added. The precipitated product was collected by filtration and purified by column chromatography eluting with methylene chloride\\/methanol\\/aqueous ammonia (150\\/8\\/1). The purified product was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazoline (70 mg, 22%) as a pale yellow solid.\",\"reactant_000\":\"OCCN1CCSCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O\",\"rxn_time\":3.5,\"reactant_003\":null,\"similarity\":0.9969648718833923,\"agent_000\":\"CCCCP(CCCC)CCCC\",\"agent_001\":\"O=C(N=NC(=O)N1CCCCC1)N1CCCCC1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][S:7][CH2:6][CH2:5]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40](O)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([O:1][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][S:7][CH2:6][CH2:5]4)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1\",\"yield_000\":22.3},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0032836198806762695,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9967163801193237,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0037235617637634277,\"rxn_id\":\"ord-ae2e2a15cfb44e3c8c0bddafaf4489b5\",\"index\":501292,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O.OCCc1ccncc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"procedure_details\":\"To a solution of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea (0.1 g, 0.24 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and triphenylphosphine (0.0944 g, 0.36 mmol) in 10 mL of dry THF was added diisopropylazo-dicarboxylate (0.0728 g, 0.36 mmol) at ambient temperature. The mixture was stirred for 2 hours. Next, additional triphenylphosphine (0.0944 g, 0.36 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and diisopropylazodicarboxylate were added and the reaction mixture further stirred at room temperature overnight. The solvent from the reaction mixture was evaporated and the crude residue was dissolved in 5.0 mL of DMSO and purified by RP-HPLC. The proper fractions were collected and concentrated to ¼ volume. The aqueous solution was neutralized with 1N NaOH and extracted with ethyl acetate (2×, 59 mL). The organic layer was dried with sodium sulfate, filtered and evaporated to dryness to afford 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyridin-4-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea as a brown solid in 44% yield. LCMS m\\/z (%)=526 (M+H 79Br, 100), 528 (M+H 81Br, 67). 1H NMR (DMSO-d6) δ: 9.33 (bs, 1H), 9.24 (bs, 1H), 8.39 (dd, J=4.44 and 1.48 Hz, 2H), 7.63 (d, J=7.28 Hz, 1H), 7.59 (s, 1H), 7.56 (dd, J=8.94 and 2.71 Hz, 2H), 7.48 (m, 1H), 7.34 (d, J=2.67, 1H), 7.31 (d, J=2.67, 1H), 7.28 (dd, J=6.88 and 4.87 Hz, 2H), 7.14 (d, J=9.05 Hz, 1H), 7.09 (d, J=5.93 Hz, 1H), 4.01-4.2 (m, 2H), 3.48 (s, 3H), 2.96-2.91 (m, 2H).\",\"reactant_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCc1ccncc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9962764382362366,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"rxn_str\":\"[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[OH:14].O[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[O:14][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1\",\"yield_000\":44.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0038225650787353516,\"rxn_id\":\"ord-33bfcf35bf734b52b59d70aa5d195f4f\",\"index\":462262,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Diethyl azodicarboxylate (2.67 ml, 17 mmol) was added dropwise to a solution of 3-morpholinopropan-1-ol (1.54 g, 10 mmol), 7-hydroxy-3,4-dihydro-6-methoxy-3-((pivaloyloxy)methyl)quinazolin-4-one (2.6 g, 8.5 mmol) and triphenylphosphine (4.45 g, 17 mmol) in methylene chloride (40 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride\\/methanol (97\\/3 followed by 95\\/5) to give 3,4-dihydro-6-methoxy-3-((pivaloyloxy)metyl)-7-(3-morpholinopropoxy)quinazolin-4-one (3.6 g, 97%).\",\"reactant_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961774349212646,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]1.O[C:24]1[CH:33]=[C:32]2[C:27]([C:28](=[O:42])[N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[N:31]2)=[CH:26][C:25]=1[O:43][CH3:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:44][O:43][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:24]=1[O:22][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[N:31]=[CH:30][N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]2=[O:42]\",\"yield_000\":97.7}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":12}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":12}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":12}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":12}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":12}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":12}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.42,"id":154,"pathId":12}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":12}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":12}],"RXN":"[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[OH:17])[N+:19](=[O:21])[O-:20])[Cl:3])[F:5].[CH2:25]1[CH2:26][O:27][CH2:28][CH2:29][N:24]1[CH2:30][CH2:31][CH2:32]O>C(C)CCP(CCCC)CCCC.ClCCl.C1CN(CCC1)C(N=NC(N2CCCCC2)=O)=O>[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:32][CH2:31][CH2:30][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[N+:19](=[O:21])[O-:20])[Cl:3])[F:5];1.7.7;Mitsunobu"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":12}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":12}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":12}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.336","depth":0,"reaction":{"label":">>0","id":0,"pathId":1849},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":1849}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":1849}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":1849}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1849}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1849}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1849}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1849}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1849}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1849}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1849}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1849}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1849}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-7.354","depth":0,"reaction":{"label":">>0","id":0,"pathId":24},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.003749549388885498,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962504506111145,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"CC(C)(C)O\",\"distance\":0.00415647029876709,\"rxn_id\":\"ord-5510c71cc19244ccb4d87f14f34e8de5\",\"index\":424079,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"procedure_details\":\"To a solution of 4-chloro-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine (40 mg, 0.15 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 1 ml) was added 3-chloro-4-fluoroaniline (22 mg, 0.15 mmol). The mixture was heated at 90° C. for 2 days. After cooling down to room temperature, the solvents were removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 100:1) to yield the title compound as a white solid (28 mg, 50%).\",\"reactant_000\":\"Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9958435297012329,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[CH:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":49.9},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.004578828811645508,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9954211711883545,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004691362380981445,\"rxn_id\":\"ord-1706282351e44a6a96c8cda1fd077e00\",\"index\":312255,\"rxn_smiles\":\"CN(C)C=O.COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Nc1c(F)cc(Cl)cc1F.[H-].[Na+]>>COc1cc2c(Nc3c(F)cc(Cl)cc3F)ncnc2cc1OCC1CCN(C)CC1\",\"procedure_details\":\"Using an analogous procedure to that described in Example 4, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (246 mg, 0.764 mmol), (prepared as described for the starting material in Example 2c), was reacted with 4-chloro-2,6-difluoroaniline (250 mg, 1.53 mmol), (see WO 97\\/30035 Example 15), in DMF (9 ml) and in the presence of sodium hydride (60%, 76.5 mg, 1.9 mmol) to give 4-(4-chloro-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (210 mg, 61%).\",\"reactant_000\":\"Nc1c(F)cc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9953086376190186,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3c(F)cc(Cl)cc3F)ncnc2cc1OCC1CCN(C)CC1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH2:28])=[C:26]([F:32])[CH:25]=1.[H-].[Na+]>CN(C=O)C>[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH:28][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[C:26]([F:32])[CH:25]=1\",\"yield_000\":61.2},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.005193650722503662,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9948063492774963,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004627108573913574,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9953728914260864,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.005324959754943848,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9946750402450562,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0059626102447509766,\"rxn_id\":\"ord-46b7aabe19fa4743a938b1aaa2a0a56d\",\"index\":662518,\"rxn_smiles\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3F)n2)c1.OCCCF>>CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCCCF)n2)c1\",\"procedure_details\":\"Starting with 4-(2,4-difluorophenyl)-N-{3-[(methylsulfonyl)methyl]phenyl}-1,3,5-triazin-2-amine (75 mg; 0.197 mmol), intermediate 42.1, and 3-fluoropropan-1-ol (59 mg; 0.736 mmol), example 54 was prepared analogously to the procedure for the preparation of example 42.\",\"reactant_000\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3F)n2)c1\",\"reactant_002\":null,\"reactant_001\":\"OCCCF\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994037389755249,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCCCF)n2)c1\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:17]=2)[N:10]=1.[F:27][CH2:28][CH2:29][CH2:30][OH:31]>>[F:8][C:6]1[CH:5]=[CH:4][C:3]([C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:17]=3)[N:10]=2)=[C:2]([O:31][CH2:30][CH2:29][CH2:28][F:27])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006279468536376953,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.993720531463623,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006436705589294434,\"rxn_id\":\"ord-855ef139e6ed4c179e58d194cc378f0b\",\"index\":33547,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.O[C@@H]1CCOC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@@H]1CCOC1\",\"procedure_details\":\"13.80 g of potassium tert-butoxide are added batchwise to a solution of 10.80 g of (R)-3-hydroxytetrahydrofuran in 100 ml of N,N-dimethylformamide while cooling with an ice bath. The reaction mixture is stirred for about one hour, then 10.40 g of 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-fluoroquinazoline are added batchwise. The cooling bath is then removed and the deep red reaction mixture is stirred for two hours at ambient temperature. For working up the reaction mixture is poured onto about 500 ml of water and neutralized with 2 N hydrochloric acid. The yellowish precipitate formed is suction filtered and dried at 70° C. in a circulating air drier. Yield: 12.80 g; melting point: 244° C.; mass spectrum (ESI−): m\\/z=403, 405 [M−H]−.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O[C@@H]1CCOC1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9935632944107056,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@@H]1CCOC1\",\"rxn_str\":\"CC(C)([O-])C.[K+].[OH:7][C@@H:8]1[CH2:12][CH2:11][O:10][CH2:9]1.[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20].Cl>CN(C)C=O.O>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:7][C@@H:8]4[CH2:12][CH2:11][O:10][CH2:9]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA ER ALL>>495","id":495},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":24}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":24}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.098,"id":460,"pathId":24}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.33,"id":92,"pathId":24}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOWKNWPFXSSYBZ","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2Cl","intrinsicScore":0.26,"id":495,"pathId":24}],"RXN":"[cH:5]1[c:6]2[c:12]([cH:13][c:14]([c:4]1[N+:2](=[O:1])[O-:3])F)[n:11][cH:10][n:9][c:7]2[Cl:8].[CH2:17]([CH2:16][OH:15])[CH2:18][Cl:19]>>[cH:5]1[c:6]2[c:12]([cH:13][c:14]([c:4]1[N+:2](=[O:1])[O-:3])[O:15][CH2:16][CH2:17][CH2:18][Cl:19])[n:11][cH:10][n:9][c:7]2[Cl:8];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.26,"id":19,"pathId":24}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":24}],"RXN":"[cH:22]1[cH:23][c:24]([c:19]([cH:20][c:21]1[NH2:26])[Cl:27])[F:25].[cH:4]1[c:3]2[c:2]([cH:12][c:6]([c:5]1[N+:13](=[O:14])[O-:15])[O:7][CH2:8][CH2:9][CH2:10][Cl:11])[n:1][cH:18][n:17][c:16]2Cl>>[cH:22]1[cH:23][c:24]([c:19]([cH:20][c:21]1[NH:26][c:16]2[c:3]3[cH:4][c:5]([c:6]([cH:12][c:2]3[n:1][cH:18][n:17]2)[O:7][CH2:8][CH2:9][CH2:10][Cl:11])[N+:13](=[O:14])[O-:15])[Cl:27])[F:25];1.3.7;Chloro"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":24}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":24}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":24}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":24}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":24}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.362","depth":0,"reaction":{"label":">>0","id":0,"pathId":328},"children":[{"depth":1,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":328}]},{"depth":7,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":328}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":328}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":328}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":328}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":328}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":328}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":328}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":328}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":328}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":328}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":328}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":328}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.396","depth":0,"reaction":{"label":">>0","id":0,"pathId":981},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":981}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":981}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":981}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":981}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":981}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":981}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":981}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":981}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":981}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":981}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":981}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-7.404","depth":0,"reaction":{"label":">>0","id":0,"pathId":335},"children":[{"depth":1,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004677474498748779,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9953225255012512,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.004711925983428955,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.995288074016571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004857063293457031,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.995142936706543,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.0048857927322387695,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9951142072677612,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":\"O\",\"distance\":0.005634188652038574,\"rxn_id\":\"ord-d91c98b6083b42d28e154dc79ab3de41\",\"index\":515521,\"rxn_smiles\":\"C1COCCN1.Cc1ccccc1.Nc1ccc(C(=O)OCCCCl)c(N)c1.O>>Nc1ccc(C(=O)OCCCN2CCOCC2)c(N)c1\",\"procedure_details\":\"A mixture of 35 ml of toluene, 4.6 g of (3-chloropropyl)-2,4-diaminobenzoate and 3.5 g of morpholine was refluxed for 10 hrs, cooled to room temperature, and poured into 70 ml of water with stirring. The precipitate was filtered, washed with hexane and dried. Recrystallization from toluene gave 2.6 g (3-morpholinopropyl)-2,4-diaminobenzoate, a white solid, mp 96° C.\",\"reactant_000\":\"Nc1ccc(C(=O)OCCCCl)c(N)c1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9943658113479614,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C(=O)OCCCN2CCOCC2)c(N)c1\",\"rxn_str\":\"C1(C)C=CC=CC=1.Cl[CH2:9][CH2:10][CH2:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=1[NH2:21].[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>O>[O:26]1[CH2:27][CH2:28][N:23]([CH2:9][CH2:10][CH2:11][O:12][C:13](=[O:22])[C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=2[NH2:21])[CH2:24][CH2:25]1\",\"yield_000\":46.3}]","literatureScore":1,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.014116823673248291,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9858831763267517,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.016109049320220947,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.983890950679779,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01629471778869629,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9837052822113037,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.017170846462249756,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9828291535377502,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.018261253833770752,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9817387461662292,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"AT ER UA TTL ALL>>173","id":173},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":335}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":335}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":335}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":335}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":335}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":335}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":486,"pathId":335}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YAIVOKCSYDYBSV","smiles":"NC1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.098,"id":173,"pathId":335}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[N+:8](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[NH2:8])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":335}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":335}],"RXN":"[cH:24]1[cH:25][c:26]([c:28]([cH:29][c:23]1[NH:22][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n+:18]([cH:17][n:16]2)[O-:21])[O:10][CH2:9][CH2:8][CH2:7]Cl)[NH2:31])[Cl:30])[F:27].[CH2:3]1[CH2:2][O:1][CH2:6][CH2:5][NH:4]1>C(CCC)CC.O=C(C)OCC.COCCOC>[cH:24]1[cH:25][c:26]([c:28]([cH:29][c:23]1[NH:22][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n+:18]([cH:17][n:16]2)[O-:21])[O:10][CH2:9][CH2:8][CH2:7][N:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)[NH2:31])[Cl:30])[F:27];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":335}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":335}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":335}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.439","depth":0,"reaction":{"label":">>0","id":0,"pathId":322},"children":[{"depth":1,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0026927590370178223,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9973072409629822,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.002873241901397705,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9971267580986023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0033760666847229004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9966239333152771,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003621220588684082,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9963787794113159,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003737330436706543,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9962626695632935,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":322}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":322}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":322}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":322}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":322}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":322}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.095,"id":486,"pathId":322}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.095,"id":9,"pathId":322}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":322}],"RXN":"[cH:21]1[cH:22][c:23]([c:25]([cH:26][c:20]1[NH:19][c:18]2[c:2]3[cH:1][c:6]([c:5]([cH:4][c:3]3[n+:14]([cH:16][n:17]2)[O-:15])[O:10][CH2:11][CH2:12][CH2:13]Cl)[N+:7](=[O:8])[O-:9])[Cl:27])[F:24].[CH2:30]1[CH2:29][O:28][CH2:33][CH2:32][NH:31]1>>[cH:21]1[cH:22][c:23]([c:25]([cH:26][c:20]1[NH:19][c:18]2[c:2]3[cH:1][c:6]([c:5]([cH:4][c:3]3[n+:14]([cH:16][n:17]2)[O-:15])[O:10][CH2:11][CH2:12][CH2:13][N:31]4[CH2:30][CH2:29][O:28][CH2:33][CH2:32]4)[N+:7](=[O:8])[O-:9])[Cl:27])[F:24];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":322}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":322}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":322}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":322}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.443","depth":0,"reaction":{"label":">>0","id":0,"pathId":1852},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":1852}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":1852}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":1852}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":1852}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1852}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1852}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1852}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1852}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1852}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1852}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1852}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1852}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-7.457","depth":0,"reaction":{"label":">>0","id":0,"pathId":918},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002493739128112793,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975062608718872,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.00285494327545166,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971450567245483,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.002886652946472168,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971133470535278,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003403782844543457,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9965962171554565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003649115562438965,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.996350884437561,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"LR ALL>>28","id":28},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006411254405975342,\"rxn_id\":\"ord-73de563950e54f3a8a473ab1f9c7e3c2\",\"index\":86652,\"rxn_smiles\":\"CN(C)C=O.O.O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12.OCC1CC1.[H-].[Na+]>>O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"procedure_details\":\"Cyclopropylmethyl alcohol (0.921 ml, 11.4 mmol) was added to a stirring suspension of NaH (455 mg, 11.4 mmol) in DMF (20 ml) under an argon atmosphere. The resulting solution was allowed to stir at RT for 20 min. 6-chloro-7-fluoro-8-nitro-9H-β-carboline (500 mg, 1.9 mmol) was added to the stirring solution and the resulting mixture was allowed to stir at RT. Upon addition of H2O, a brown solid precipitated out which was filtered to give the desired 6-chloro-7-cyclopropylmethyoxy-8-nitro-9H-β-carboline (510 mg, 85%). 1H-NMR (300 MHz, DMSO-d6): δ 0.35 (m, 2H), 0.59 (m, 2H), 1.32 (m, 1H), 4.04 (d, 2H), 8.21 (d, 1H), 8.46 (d, 1H), 8.90 (s, 1H), 9.02 (s, 1H), 12.32 (b, 1H). Retention Time (LC, method: ammonium acetate standard): 2.63 min. MS (M+H+): 318.\",\"reactant_000\":\"O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12\",\"reactant_002\":null,\"reactant_001\":\"OCC1CC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9935887455940247,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1F)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1[O:5][CH2:4][CH:1]1[CH2:3][CH2:2]1)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1\",\"yield_000\":84.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006817042827606201,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9931829571723938,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.007981956005096436,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9920180439949036,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00798940658569336,\"rxn_id\":\"ord-e13729e09b02453d8b2ae8502f41e869\",\"index\":593117,\"rxn_smiles\":\"CC(C)(C)[O-].CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-].OCC(F)F.[K+]>>CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"procedure_details\":\"The subtitle compound is prepared from N-(4-bromophenyl)-2-fluoro-4-methylamino-5-nitro-benzamide, 2,2-difluoroethanol and KOtBu in analogy to example 1e.\",\"reactant_000\":\"CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9920105934143066,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2F)=[CH:4][CH:3]=1.[F:23][CH:24]([F:27])[CH2:25][OH:26].CC([O-])(C)C.[K+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2[O:26][CH2:25][CH:24]([F:27])[F:23])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008773088455200195,\"rxn_id\":\"ord-c07b2acbc69f47289d653f004b6d071c\",\"index\":64408,\"rxn_smiles\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12.Cl.OCC(F)F.[H-].[Na+]>>COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"procedure_details\":\"Sodium hydride (1.21 g, 30 mmol, as a 60% suspension in mineral oil) was charged into a round bottom flask equipped with magnetic stirring and a nitrogen blanket, washed twice with 10 mL hexanes, dried of residual hexanes under a nitrogen stream, and suspended in 1,2-dimethoxyethane (20 mL). After cooling in an ice bath to about 10° C., 2-fluoro-6-trifluoromethyl-N-(5, 8-di-methoxy[ 1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide (4.21 g, about 98.5% purity, 10 mmol) was added over about 5 min, rinsing in with 1 mL 1,2-dimethoxyethane. A slight exotherm to about 13° C. occurred. Continued ice bath cooling lowered temperature to about 6° C. over about 10 min. To the off-white suspension was added 2,2-difluoroethanol (0.815 niL, 13 mmol) over about 5 min. A slight exotherm to about 13° C. occurred. The light tan suspension was stirred at about 5-10° C. for about 1 hr, then the ice bath was removed. The temperature peaked at about 28° C. (about 2° C. above room temperature) about 0.5 hr later. The tan suspension was stirred overnight (about 20 hr total reaction time), then worked up by addition of the reaction mixture over about 7 min into 5% hydrochloric acid (80 mL, 112 mmol) at about 5-10° C. with ice bath cooling. The suspension was stirred about 18 min at about 9° C., then filtered, washed twice with 15 mL water each, washed twice with 15 mL methanol each, air-dried for about 2 hr, and finally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide to afford the product as a white powder (4.34 g, about 92.8% purity, 8.3 mmol, about 83% yield).\",\"reactant_000\":\"OCC(F)F\",\"reactant_002\":null,\"reactant_001\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9912269115447998,\"agent_000\":\"Cl\",\"agent_001\":\"[H-]\",\"agent_002\":\"[Na+]\",\"temperature\":10.0,\"product_000\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"rxn_str\":\"[H-].[Na+].F[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15].[F:31][CH:32]([F:35])[CH2:33][OH:34].Cl>>[F:31][CH:32]([F:35])[CH2:33][O:34][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:11])([F:12])[F:13])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15]\",\"yield_000\":83.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>228","id":228},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.0052683353424072266,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9947316646575928,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005525708198547363,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944742918014526,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.005835771560668945,\"rxn_id\":\"ord-6569ee74ee084f45aee0cc6bab387a3a\",\"index\":556261,\"rxn_smiles\":\"BrBr.CC(=O)O.Nc1ccc2nc(C(F)(F)F)[nH]c2c1>>Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"procedure_details\":\"To a solution of 3.2 g (16 mmol) of 2-trifluoromethyl-5-aminobenzimidazole in 50 ml of AcOH was added 0.34 ml (6.6 mmol) of Br2 dropwise and resulting reaction mixture was stirred for 1 h at 25° C. The reaction mixture was concentrated in vacuo and purified on silica gel column chromatography (10% MeOH\\/CHCl3) to yield 1.7 g (6.2 mmol, 94%) of the desired product.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.994164228439331,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"rxn_str\":\"[F:1][C:2]([F:14])([F:13])[C:3]1[NH:4][C:5]2[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[Br:15]Br>CC(O)=O>[F:14][C:2]([F:1])([F:13])[C:3]1[NH:4][C:5]2[C:11]([Br:15])=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1\",\"yield_000\":93.9},{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.005841076374053955,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994158923625946,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005856215953826904,\"rxn_id\":\"ord-1d443c1852a24a44bc10d8df0c32bd94\",\"index\":784164,\"rxn_smiles\":\"BrBr.ClC(Cl)Cl.Nc1ccc2ncsc2c1>>Nc1ccc2ncsc2c1Br\",\"procedure_details\":\"To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67 mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27 mmol) in CHCl3 (10 ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5:1) to give 7-bromobenzo[d]thiazol-6-amine (80 mg, 80%).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncsc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941437840461731,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ncsc2c1Br\",\"rxn_str\":\"[S:1]1[C:5]2[CH:6]=[C:7]([NH2:10])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Br:11]Br>C(Cl)(Cl)Cl>[Br:11][C:6]1[C:5]2[S:1][CH:2]=[N:3][C:4]=2[CH:9]=[CH:8][C:7]=1[NH2:10]\",\"yield_000\":129.3}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>528","id":528},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":918}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.3,"id":159,"pathId":918}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.3,"id":522,"pathId":918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CUHXEXBIVQEVJM","smiles":"[O-][N+](=O)C1=CC2=C(N=CN=C2NC2=CC(Cl)=C(F)C=C2)C(Br)=C1F","intrinsicScore":0.33,"id":528,"pathId":918}],"RXN":"[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([cH:11][c:3]3[n:2][cH:1][n:23]2)[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22].[Br:24]Br>>[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([c:11]([c:3]3[n:2][cH:1][n:23]2)[Br:24])[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22];10.1.1;Bromination"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.33,"id":43,"pathId":918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"JWFJQOCJPWGBQR","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C(Br)=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1","intrinsicScore":0.71,"id":228,"pathId":918}],"RXN":"[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])F)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>>[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":918}],"RXN":"[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:26])[F:30]>>[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:26])[F:30];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":918}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":918}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":918}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-7.469","depth":0,"reaction":{"label":">>0","id":0,"pathId":331},"children":[{"depth":1,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":331}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":331}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":331}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":331}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":331}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":331}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":331}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":331}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":331}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":331}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":331}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":331}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":331}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.474","depth":0,"reaction":{"label":">>0","id":0,"pathId":64},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.8,"literature":"[{\"solvent_000\":\"CCC(=O)CC\",\"solvent_001\":null,\"distance\":0.008867144584655762,\"rxn_id\":\"ord-e136e5aa10ab49daad3600b6e97cea77\",\"index\":127077,\"rxn_smiles\":\"CCC(=O)CC.O=C(Nc1ccc(C#CCCCCl)cc1)C(F)(F)F.[Br-].[Li+]>>O=C(Nc1ccc(C#CCCCBr)cc1)C(F)(F)F\",\"procedure_details\":\"A solution of Intermediate 25 (approximately 10 mmol) in 3-pentanone (200 mL) was treated with lithium bromide (10 eq, 100 mmol). The mixture was heated to reflux for 16 hours, followed by concentration to dryness under reduced pressure. The residue was taken up in ethyl acetate and washed with water. The concentrated organic phase was taken up again in 3-pentanone (200 mL) and heated to reflux for four hours in the presence of lithium bromide (10 eq, 100 mmol). The mixture was concentrated to dryness under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude product was purified via automated flash silica gel chromatography, using a 40 g SiliSep flash column (hexanes\\/ethyl acetate). Concentration of the desired fractions under reduced pressure provided the title compound as an off-white solid. ES\\/MS calcd. for C13H12BrF3NO+ 334.0. found m\\/z=334.1 (M+H)+.\",\"reactant_000\":\"[Br-]\",\"reactant_002\":null,\"reactant_001\":\"O=C(Nc1ccc(C#CCCCCl)cc1)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9911328554153442,\"agent_000\":\"[Li+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(Nc1ccc(C#CCCCBr)cc1)C(F)(F)F\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=1.[Br-:20].[Li+]>CCC(=O)CC>[Br:20][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CCCCCCC\",\"distance\":0.01181262731552124,\"rxn_id\":\"ord-fc2f0be483fc4e008a53d25faa8aa40b\",\"index\":519908,\"rxn_smiles\":\"CCCCCCC.COC(=O)C=CCCCCl.O.[Br-].[Li+]>>COC(=O)C=CCCCBr\",\"procedure_details\":\"In an atmosphere of nitrogen, 6-chloro-2-hexenoic acid methyl ester (4Cl); 188.8 g {GC purity; 83.6%, pure amount; 157.9 g (0.971 mol)}, lithium bromide (126.5 g, 1.457 mol) and heptane (16 ml) were added to a 500 ml capacity flask, followed by stirring for 6 hours under heptane reflux. After completion of the reaction, heptane was added as an extraction solvent and water was added thereto to separate the organic layer. The solvent was evaporated under a reduced pressure using an evaporator, and then the residue was distilled under a reduced pressure (70 to 80° C.\\/0.1 ton) to obtain 6-bromo-2-hexenoic acid methyl ester (4Br); 203.4 g {GC purity; 82.3%, pure amount (4Br); 167.5 g (0.809 mol, yield 83%\\/(4Cl)}.\",\"reactant_000\":\"COC(=O)C=CCCCCl\",\"reactant_002\":null,\"reactant_001\":\"[Br-]\",\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9881873726844788,\"agent_000\":\"[Li+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)C=CCCCBr\",\"rxn_str\":\"[CH3:1][O:2][C:3](=[O:10])[CH:4]=[CH:5][CH2:6][CH2:7][CH2:8]Cl.[Br-:11].[Li+].CCCCCCC>O>[CH3:1][O:2][C:3](=[O:10])[CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][Br:11]\",\"yield_000\":83.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.01231682300567627,\"rxn_id\":\"ord-9a195e467a3941338ab24f7942719c1a\",\"index\":741083,\"rxn_smiles\":\"Br.C1COCCO1.CC(=O)O.Cl.O=C(O)CCC(F)(F)CCl>>O=C(O)CCC(F)(F)CBr\",\"procedure_details\":\"A solution of the product from Step 2 (14.2 g, 57.9 mmol) in a 5:1 methanol\\/H2O solvent mixture (240 mL) was stirred as lithium hydroxide mono-hydrate (7.29 g, 174 mmol) was added. After stirring at room temperature for 2 h, the reaction volume was concentrated and the remainder was partitioned between dichloromethane (300 mL) and 4N HCl (100 mL). The organic phase was separated, dried over sodium sulfate and concentrated to afford 8.60 g (68%) of the product as a white solid. This product contains 33% of the 5-chloro adduct. 1H NMR (400 MHz, Chloroform-d) δ 3.67 (t, 0.6H), 3.53 (t, 1.4H), 2.62 (t, 2H), 2.43-2.28 (m, 2H). 5-Chloro-4,4-difluoro-pentanoic acid can be prepared in an analogous fashion by substituting HCl in dioxane for the HBr in acetic acid in Step 1.\",\"reactant_000\":\"O=C(O)CCC(F)(F)CCl\",\"reactant_002\":null,\"reactant_001\":\"Br\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9876831769943237,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(O)CCC(F)(F)CBr\",\"rxn_str\":\"Cl[CH2:2][C:3]([F:10])([F:9])[CH2:4][CH2:5][C:6]([OH:8])=[O:7].Cl.[BrH:12]>O1CCOCC1.C(O)(=O)C>[Br:12][CH2:2][C:3]([F:10])([F:9])[CH2:4][CH2:5][C:6]([OH:8])=[O:7]\",\"yield_000\":null},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.014212489128112793,\"rxn_id\":\"ord-0017813294b64f21afa9f508a322291c\",\"index\":21443,\"rxn_smiles\":\"CC(C)=O.Cc1c(F)cccc1CC(=O)CCl.[Br-].[Li+]>>Cc1c(F)cccc1CC(=O)CBr\",\"procedure_details\":\"The compound of step 1 (3.20 g, 15.95 mmol) was dissolved in acetone (70 ml), and lithium bromide (11.08 g, 127.59 mmol) was added. The mixture was stirred overnight. The solvent was evaporated, the resulting solid was dissolved in EA and the solution washed twice with water followed by a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated to dryness. 3.66 g of the title compound were obtained as a white powder.\",\"reactant_000\":\"Cc1c(F)cccc1CC(=O)CCl\",\"reactant_002\":null,\"reactant_001\":\"[Br-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9857875108718872,\"agent_000\":\"[Li+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1c(F)cccc1CC(=O)CBr\",\"rxn_str\":\"Cl[CH2:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[CH3:12].[Br-:14].[Li+]>CC(C)=O>[Br:14][CH2:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[CH3:12]\",\"yield_000\":93.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCOCC\",\"distance\":0.014679491519927979,\"rxn_id\":\"ord-f6c0f997f4574b7d99e3a5984f3dc778\",\"index\":156879,\"rxn_smiles\":\"C1CCOC1.CCCCCC#CCCCCl.CCOCC.[Br-].[Li+]>>CCCCCC#CCCCBr\",\"procedure_details\":\"1-Bromodec-4-yne was prepared from 1-chlorodec-4-yne. The 1-chlorodec-4-yne (10.6 g, 61 mmol) and 25 g of lithium bromide were refluxed in 80 ml of THF for 21 hours. The conversion was 74%. Ether was added, the reaction mixture was washed with water (2×) and brine, dried over magnesium sulfate and stripped. The product was dissolved in 70 ml of THF and refluxed for 8 hours with an additional 25 g of lithium bromide. This gave 95% conversion of the chloride to the bromide. The same workup provided 11.36 g of 1-bromodec-4-yne.\",\"reactant_000\":\"CCCCCC#CCCCCl\",\"reactant_002\":null,\"reactant_001\":\"[Br-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.985320508480072,\"agent_000\":\"[Li+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCCCCC#CCCCBr\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][C:5]#[C:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[Br-:12].[Li+].CCOCC>C1COCC1>[Br:12][CH2:2][CH2:3][CH2:4][C:5]#[C:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]\",\"yield_000\":null}]","literatureScore":0.99,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":64}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":64}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":64}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":64}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":165,"pathId":64}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"TTL ALL>>247","id":247},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CPELXLSAUQHCOX","smiles":"Br","intrinsicScore":0.046,"id":247,"pathId":64}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":64}],"RXN":"[cH:11]1[cH:12][c:13]([c:14]([cH:16][c:10]1[NH:9][c:8]2[c:7]3[cH:6][c:2]([c:1]([cH:22][c:21]3[n:20][cH:19][n:18]2)[O:23][CH2:24][CH2:25][CH2:26]Cl)[N+:3](=[O:4])[O-:5])[Cl:15])[F:17].[BrH:27]>C1COCCO1.O.[Na+].[OH-]>[cH:11]1[cH:12][c:13]([c:14]([cH:16][c:10]1[NH:9][c:8]2[c:7]3[cH:6][c:2]([c:1]([cH:22][c:21]3[n:20][cH:19][n:18]2)[O:23][CH2:24][CH2:25][CH2:26][Br:27])[N+:3](=[O:4])[O-:5])[Cl:15])[F:17];9.7.179;Chloro"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":64}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":64}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":64}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":64}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":64}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.478","depth":0,"reaction":{"label":">>0","id":0,"pathId":1872},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.2,"literature":"[{\"solvent_000\":\"CCO\",\"solvent_001\":\"O\",\"distance\":0.03514432907104492,\"rxn_id\":\"ord-ac830d54b7724a8b93da7678034827fa\",\"index\":571122,\"rxn_smiles\":\"CCO.Cc1cc(Br)c2nc(O)c[n+]([O-])c2c1.O.O=S([O-])S(=O)[O-].[Na+].[Na+]>>Cc1cc(Br)c2nc(O)cnc2c1\",\"procedure_details\":\"The title compound of Step C (25 g, 98 mmol) and sodium dithionite (38 g, 220 mmol) were suspended in a mixture of ethanol (1000 mL) and water (200 mL) at room temperature. After 1 h, most of the solvent was removed under reduced pressure. The residue was diluted with water and acidified with hydrochloric acid. Insolubles were removed by filtration. The filtrate was extracted twice with methylene chloride. The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure to afford the title compound of Step D as a tan\\/yellow solid (15.29 g, 65%). 1H NMR (CDCl3): δ2.37 (s,3H), 7.5 (d,2H), 8.15 (s, 1H), 9.8 (br s, 1H).\",\"reactant_000\":\"Cc1cc(Br)c2nc(O)c[n+]([O-])c2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9648556709289551,\"agent_000\":\"O=S([O-])S(=O)[O-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Br)c2nc(O)cnc2c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([OH:12])[CH:8]=[N+:7]2[O-].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([OH:12])[CH:8]=[N:7]2\",\"yield_000\":65.3},{\"solvent_000\":\"ClP(Cl)Cl\",\"solvent_001\":\"ClC(Cl)Cl\",\"distance\":0.03644132614135742,\"rxn_id\":\"ord-4ee3d8d301824f80b57afcbb6894ed3d\",\"index\":186003,\"rxn_smiles\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC.ClC(Cl)Cl.ClP(Cl)Cl>>COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"procedure_details\":\"A solution of N-oxide 3 (10 mM) and phosphorus trichloride (30 mM) in anhydrous chloroform (100 ml) was refluxed for 7 h. Solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulphate and then evaporated under reduced pressure. The residue was recrystallized from isopropanol to provide the title dimethyl quinoline-2,3-dicarboxylate 7 as an off white (or light yellow) powder.\",\"reactant_000\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9635586738586426,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"rxn_str\":\"[N+:1]1([O-])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16].P(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1=CCCCC1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.04215782880783081,\"rxn_id\":\"ord-e79e74c481414470aec1b7e2b799dffb\",\"index\":735026,\"rxn_smiles\":\"C1=CCCCC1.CC(C)O.COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1.[Pd]>>COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"procedure_details\":\"A mixture of 7-({2-[(4-methoxybenzyl)amino]-1-oxidopyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (21.1 g, 0.0502 mol), cyclohexene (100 mL, 0.9 mol) and Pd (10% on Carbon, 4.5 g) in isopropyl alcohol (400 mL, 5 mol) was heated at 85° C. overnight. Additional catalyst (2.5 g) and cyclohexene (30 mL) were added. The mixture was heated at 90° C. overnight and then filtered. The filtrate was concentrated to give 7-({2-[(4-methoxybenzyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid which was used in the next step without purification. LCMS ES+ 405.7\",\"reactant_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9578421711921692,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":85.0,\"product_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N+:10]=2[O-])=[CH:5][CH:4]=1.C(O)(C)C>[Pd].C1CCCCC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[CH:30][CH:31]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.04627472162246704,\"rxn_id\":\"ord-41f86ab7b419465b93bad7cb1b735ee9\",\"index\":112985,\"rxn_smiles\":\"CC(=O)O.COc1cc[n+]([O-])c(NCCN(C(C)C)C(C)C)c1.[Fe]>>COc1ccnc(NCCN(C(C)C)C(C)C)c1\",\"procedure_details\":\"2-(2-diisopropylaminoethylamino)-4-methoxypyridine-N-oxide (4.3 g., 15 mmole) dissolved in glacial acetic acid (32 ml.) is refluxed with iron powder (8.2 g.) for three hours. The reaction mixture is filtered to remove insoluble salts and then the solvent evaporated. The residue is dissolved in methanol, treated with excess potassium hydroxide pellets and filtered to remove more insoluble salts. The concentrate solution is dissolved in chloroform, washed with water, dried over sodium sulfate, filtered through a pad of charcoal and evaporated to give oily product.\",\"reactant_000\":\"COc1cc[n+]([O-])c(NCCN(C(C)C)C(C)C)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.953725278377533,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccnc(NCCN(C(C)C)C(C)C)c1\",\"rxn_str\":\"[CH:1]([N:4]([CH:17]([CH3:19])[CH3:18])[CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][N+:9]=1[O-])([CH3:3])[CH3:2]>C(O)(=O)C.[Fe]>[CH:17]([N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][N:9]=1)([CH3:18])[CH3:19]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.05018347501754761,\"rxn_id\":\"ord-983f4b85a4c94a6e873248f98cfebcb3\",\"index\":368215,\"rxn_smiles\":\"CCCc1cc(OC)cc[n+]1[O-].O=S(=O)(O)O.[Zn]>>CCCc1cc(OC)ccn1\",\"procedure_details\":\"A solution of 4-methoxy-2-n-propylpyridine-N-oxide (59.3 g, 0.355 mol) in 800 ml of 1 M sulfuric acid was stirred and heated to 70-80° C. Zinc dust (140.0 g, 214 mol) was added in portions over four hours. When the addition was complete, heating was continued for a further eight hours. The resulting precipitate was filtered off and washed with water. The filtrate was made strongly alkaline by addition of a 32% sodium hydroxide solution and extracted with dichloromethane (3×250 ml). The extracts were combined, dried with sodium sulfate, filtered and evaporated to a yellow oil. Distillation (0.1-0.2 mbar, 44-46° C.) afforded 46.1 g (86%) of 4-methoxy-2-n-propylpyridine as a colourless oil. 1H-NMR (CDCl3, 200 MHz) δ: 0.99 (t, 3H), 1.75 (sext, 2H), 2.72 (t, 2H), 3.81 (s, 3H), 6.10-6.18 (m, 2H), 8.35 (d, 1H).\",\"reactant_000\":\"CCCc1cc(OC)cc[n+]1[O-]\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9498165249824524,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[Zn]\",\"agent_002\":null,\"temperature\":75.0,\"product_000\":\"CCCc1cc(OC)ccn1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N+:6]([O-])=[C:5]([CH2:10][CH2:11][CH3:12])[CH:4]=1>S(=O)(=O)(O)O.[Zn]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:10][CH2:11][CH3:12])[CH:4]=1\",\"yield_000\":85.9}]","literatureScore":0.96,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.014116823673248291,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9858831763267517,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.016109049320220947,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.983890950679779,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01629471778869629,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9837052822113037,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.017170846462249756,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9828291535377502,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.018261253833770752,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9817387461662292,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"AT ER UA TTL ALL>>173","id":173},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1872}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1872}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":1872}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":1872}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":1872}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":1872}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":486,"pathId":1872}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YAIVOKCSYDYBSV","smiles":"NC1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.24,"id":173,"pathId":1872}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[N+:8](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[NH2:8])[Cl:18])[F:20];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1872}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCCCl)N)Cl)F>C(C)O.Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCCl)N)Cl)F;0.0;Unrecognized"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1872}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1872}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1872}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1872}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-7.523","depth":0,"reaction":{"label":">>0","id":0,"pathId":36},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":36}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":36}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":36}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":36}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":36}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":36}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":36}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":36}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":36}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":36}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":36}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":36}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.56","depth":0,"reaction":{"label":">>0","id":0,"pathId":19},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 UA 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ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":19}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":19}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":19}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":19}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":19}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":19}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":19}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":19}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":19}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.597","depth":0,"reaction":{"label":">>0","id":0},"children":[{"depth":1,"reaction":{"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"label":"TTL ALL>>167","id":167},"children":[{"depth":4,"reaction":{"label":"ER UA TTL ALL>>672","id":672},"children":[{"depth":5,"reaction":{"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[],"molecules":[{"commercial":false,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","id":159,"pathId":88}]}],"molecules":[{"commercial":false,"inchi":"FCEJYNJLOZLCCR","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1OCCCN=[N+]=[N-]","id":672,"pathId":88}]}],"molecules":[{"commercial":false,"inchi":"NGGHYTSBRHGJPA","smiles":"NCCCOC1=C(C=C2C(NC3=CC=C(F)C(Cl)=C3)=NC=NC2=C1)[N+]([O-])=O","id":167,"pathId":88}]}],"molecules":[{"commercial":false,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","id":23,"pathId":88}]}],"molecules":[{"commercial":false,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","id":5,"pathId":88}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":88}]},{"pathScore":"-7.619","depth":0,"reaction":{"label":">>0","id":0,"pathId":1858},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004968404769897461,\"rxn_id\":\"ord-67cd89c92ec043eaa8c192a52c6055e1\",\"index\":71209,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)c(F)c2)cc1>>N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"procedure_details\":\"The product from Example 167A and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (99% yield). 1HNMR (300 MHz, CDCl3) δ2.30 (m, 2H), 3.80 (m, 2H), 4.25 (m, 2H), 7.12-7.75 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)c(F)c2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950315952301025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)=[CH:3][C:2]=1[F:1]\",\"yield_000\":99.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005435526371002197,\"rxn_id\":\"ord-593d5907c892416383020940bf139801\",\"index\":592545,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)cc2)cc1F>>N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"procedure_details\":\"The product from Example 166B and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (98% yield). 1HNMR (300 MHz, CDCl3) δ2.25 (m, 2H), 3.80 (m, 2H), 4.20 (m, 2H), 7.00-7.65 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)cc2)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945644736289978,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([F:1])[CH:3]=2)=[CH:11][CH:12]=1\",\"yield_000\":98.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005583524703979492,\"rxn_id\":\"ord-f2089ee29c9c49d6bda509b96fde9e15\",\"index\":355059,\"rxn_smiles\":\"ClCCCBr.Cn1ncc(-c2ccc(O)cc2)cc1=O>>Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"procedure_details\":\"5-[4-(3-Chloro-propoxy)-phenyl]-2-methyl-2H-pyridazin-3-one was prepared from 5-(4-hydroxy-phenyl)-2-methyl-2H-pyridazin-3-one with 1-bromo-3-chloro-propane using the procedure described in Example 86 Step 3; Mp 90-91° C.; MS m\\/z 279 (M+H).\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"Cn1ncc(-c2ccc(O)cc2)cc1=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944164752960205,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0058318376541137695,\"rxn_id\":\"ord-0943760d2d71451cb76c1188d0d02866\",\"index\":410217,\"rxn_smiles\":\"ClCCCBr.O=C1NCCn2c1cc1cc(O)cnc12>>O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"procedure_details\":\"The title compound was synthesized in analogy to example 2, intermediate, from 7-hydroxy-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one (example 84, intermediate a) and 1-bromo-3-chloropropane, to give the desired product as a light yellow solid (80%).\",\"reactant_000\":\"O=C1NCCn2c1cc1cc(O)cnc12\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941681623458862,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"rxn_str\":\"[OH:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1\",\"yield_000\":80.0},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.006563842296600342,\"rxn_id\":\"ord-cbbf3a06c7d04efaab9b011975b2bcaf\",\"index\":118810,\"rxn_smiles\":\"CC(C)=O.ClCCCBr.O=C1CSc2cc(O)ccc2N1>>O=C1CSc2cc(OCCCCl)ccc2N1\",\"procedure_details\":\"After a mixture consisting of 7-hydroxy-3,4-dihydro-2H-1,4-benzothiazin-3-one (1.812 g, 10 mmol), 1bromo-3-chloropropane (2.362 g, 15 mmol), potassium carbate (4.146 g, 30 mmol) and acetone (40 mmol) was heated under reflux and stirring for 24 hours, insolube matter was filtered off, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel column (developer: chloroform) to purify the same, and was then recrystallized from acetone. The title compound (1.300 g) was obtained as yellow leaflets (yield: 50.4%).\",\"reactant_000\":\"O=C1CSc2cc(O)ccc2N1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9934361577033997,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CSc2cc(OCCCCl)ccc2N1\",\"rxn_str\":\"[OH:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.Br[CH2:14][CH2:15][CH2:16][Cl:17].CC(C)=O>>[Cl:17][CH2:16][CH2:15][CH2:14][O:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1\",\"yield_000\":50.4}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1858}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1858}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":1858}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":1858}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.43,"id":154,"pathId":1858}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":4,"reaction":{"label":"TTL ALL T5 UA ER ALL>>90","id":90},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MFESCIUQSIBMSM","smiles":"ClCCCBr","intrinsicScore":0.43,"id":90,"pathId":1858}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1858}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:26]([CH2:25][Cl:24])[CH2:27]Br>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:23][CH2:27][CH2:26][CH2:25][Cl:24])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.9;Williamson"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1858}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1858}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1858}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1858}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1858}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-7.779","depth":0,"reaction":{"label":">>0","id":0,"pathId":1150},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.002605915069580078,\"rxn_id\":\"ord-33bfcf35bf734b52b59d70aa5d195f4f\",\"index\":462262,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Diethyl azodicarboxylate (2.67 ml, 17 mmol) was added dropwise to a solution of 3-morpholinopropan-1-ol (1.54 g, 10 mmol), 7-hydroxy-3,4-dihydro-6-methoxy-3-((pivaloyloxy)methyl)quinazolin-4-one (2.6 g, 8.5 mmol) and triphenylphosphine (4.45 g, 17 mmol) in methylene chloride (40 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride\\/methanol (97\\/3 followed by 95\\/5) to give 3,4-dihydro-6-methoxy-3-((pivaloyloxy)metyl)-7-(3-morpholinopropoxy)quinazolin-4-one (3.6 g, 97%).\",\"reactant_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9973940849304199,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]1.O[C:24]1[CH:33]=[C:32]2[C:27]([C:28](=[O:42])[N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[N:31]2)=[CH:26][C:25]=1[O:43][CH3:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:44][O:43][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:24]=1[O:22][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[N:31]=[CH:30][N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]2=[O:42]\",\"yield_000\":97.7},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.002660691738128662,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9973393082618713,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0028061866760253906,\"rxn_id\":\"ord-5110d57e891a4de49f8c2e81d8f9fd03\",\"index\":533282,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Cl)ncnc2cc1O.ClCCl.OCCCN1CCN(CCF)CC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1\",\"procedure_details\":\"A suspension of 4-chloro-7-hydroxy-6-methoxyquinazoline (202 mg, 0.96 mmol), (prepared as described for the starting material in Example 4), in methylene chloride (10 ml) was treated with triphenylphosphine (352 mg, 1.35 mmol), 3-[4-(2-fluoroethyl)piperazin-1-yl)propan-1-ol (200 mg, 1.06 mmol), (prepared as described for the starting material in Example 27), and diisopropyl azodicarboxylate (226 mg, 1.15 mmol) and the mixture stirred at ambient temperature for 2 hours. The crude reaction mixture was loaded onto a silica column and eluted using methylene chloride\\/methanol (95\\/5). The relevant fractions were combined and evaporated under vacuum to give 4-chloro-7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxyquinazoline (208 mg, 57%) as a white solid.\",\"reactant_000\":\"OCCCN1CCN(CCF)CC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Cl)ncnc2cc1O\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971938133239746,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][CH2:45]O)[CH2:39][CH2:38]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:45][CH2:44][CH2:43][N:40]3[CH2:39][CH2:38][N:37]([CH2:36][CH2:35][F:34])[CH2:42][CH2:41]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1\",\"yield_000\":56.6},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0032477378845214844,\"rxn_id\":\"ord-2b0d95981c8a4f6c969e32364dd2b807\",\"index\":711622,\"rxn_smiles\":\"CCOC(=O)\\/N=N\\/C(=O)OCC.COc1cc2ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Crude cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(6-hydroxy-7-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (333 mg, 0.66 mmol), PS-PPh3 resin, (loading=2.33 mmol\\/g, 797 mg, 1.86 mmol), 3-morpholin-4-yl-propan-1-ol (0.26 ml, 1.88 mmol), and DEAD (0.31 ml, 1.91 mmol) were combined in CH2Cl2 (10 ml) and stirred at room temperature for 1-2 hrs. The reaction mixture was filtered and the resin thoroughly washed with CH2Cl2. The filtrate was concentrated in vacuo and the resulting residue was dissolved in EtOAc and washed with H2O (4×) and sat'd NaCl (1×) and then extracted with 1N HCl (3×). The combined 1N HCl extractions were washed with EtOAc (2×). The acidic aqueous phase was then basified with 1N NaOH and extracted with EtOAc (3×). The combined EtOAc extractions were washed with H2O (1×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The resulting residue was purified by preparative reverse phase HPLC (25 mM NH4OAc\\/acetonitrile) and the pure fractions were lyophilized to give cyclopropane-1,1-dicarboxylic acid {3-fluoro-4-[7-methoxy-6-(3-morpholin-4-yl-propoxy)-quinazolin-4-yloxy]-phenyl}-amide(4-fluoro-phenyl)-amide (42.6 mg, 10%). 1H NMR (400 MHz, DMSO-d6): d 10.37 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.84 (m, 1H), 7.65 (m, 2H), 7.58 (s, 1H), 7.43 (m, 3H), 7.16 (t, 2H), 4.27 (m, 2H), 4.00 (s, 3H), 3.60 (m, 6H), 2.39 (m, 4H), 1.99 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.1.\",\"reactant_000\":\"COc1cc2ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9967522621154785,\"agent_000\":\"CCOC(=O)\\/N=N\\/C(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([O:35][CH3:36])=[C:31]([OH:34])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[N:57]1([CH2:63][CH2:64][CH2:65]O)[CH2:62][CH2:61][O:60][CH2:59][CH2:58]1.CCOC(\\/N=N\\/C(OCC)=O)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([O:35][CH3:36])=[C:31]([O:34][CH2:65][CH2:64][CH2:63][N:57]6[CH2:62][CH2:61][O:60][CH2:59][CH2:58]6)[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:6][CH:7]=1\",\"yield_000\":10.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0033155083656311035,\"rxn_id\":\"ord-e0b0f01cfc8846efa4465e6a5288872d\",\"index\":23488,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (1.5 g, 2.96 mmol), 4-(3-hydroxypropyl)morpholine (0.623 mL, 4.5 mmol), triphenylphosphine (1.18 g, 4.5 mmol), and dichloromethane (50 mL) was added diisopropyl azodicarboxylate (0.886 mL, 4.5 mmol). The mixture was stirred at room temperature for 16 h, monitored by LCMS. After removal of solvent, the crude mixture was separated by flash column chromatography (silica), eluting with 5% methanol in dichloromethane to give N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N\\u2032-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (890 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.36 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.83 (m, 1H), 7.64 (m, 2H), 7.57 (s, 1H), 7.44 (m, 3H), 7.18 (t, 2H), 4.27 (m, 2H), 3.99 (s, 3H), 3.61 (m, 6H), 2.40 (m, 4H), 2.01 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.3.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9966844916343689,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:37][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:36][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1\",\"yield_000\":47.5}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003694891929626465,\"rxn_id\":\"ord-6cdd1bd8891a45388bc6e0ac1fc81cc2\",\"index\":772867,\"rxn_smiles\":\"Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1.O=C(O)CCOc1ccccc1>>O=C(CCOc1ccccc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"procedure_details\":\"Following the procedure of Example 2, making variations only as required to use 3-phenoxypropionic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (52% yield). 1H NMR (300 MHz, CDCl3) δ 10.08, 8.40, 7.74, 7.61, 7.55, 7.34, 7.26-7.22, 7.05, 6.93, 6.88, 4.34, 4.01-3.96, 3.92-3.86, 3.68-3.60, 3.55-3.53, 3.29-3.27, 3.08. MS (ES+) m\\/z 500.3 (M+1).\",\"reactant_000\":\"O=C(O)CCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963051080703735,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCOc1ccccc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"rxn_str\":\"[O:1]([CH2:8][CH2:9][C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:13][C:14]1[N:19]=[N:18][C:17]([N:20]2[CH2:25][CH2:24][N:23]([C:26]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]([F:37])([F:36])[F:35])=[O:27])[CH2:22][CH2:21]2)=[CH:16][CH:15]=1>>[O:1]([CH2:8][CH2:9][C:10]([NH:13][C:14]1[N:19]=[N:18][C:17]([N:20]2[CH2:21][CH2:22][N:23]([C:26](=[O:27])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]([F:37])([F:36])[F:35])[CH2:24][CH2:25]2)=[CH:16][CH:15]=1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0039550065994262695,\"rxn_id\":\"ord-8b2d821562254b1292753e08ae69595b\",\"index\":328739,\"rxn_smiles\":\"Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1.O=C(O)CCc1ccc(F)cc1>>O=C(CCc1ccc(F)cc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"procedure_details\":\"Following the procedure of Example 2, making variations only as required to use 3-(4-fluorophenyl)propionic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white solid (58.5% yield). 1H NMR (300 MHz, CDCl3) δ 10.33, 8.40, 7.78, 7.67, 7.60, 7.36, 7.14, 7.08, 6.85, 3.90, 3.51, 3.20, 3.02, 2.92. MS (ES+) m\\/z 502.7 (M+1).\",\"reactant_000\":\"Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"reactant_002\":null,\"reactant_001\":\"O=C(O)CCc1ccc(F)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960449934005737,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCc1ccc(F)cc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.[NH2:13][C:14]1[N:19]=[N:18][C:17]([N:20]2[CH2:25][CH2:24][N:23]([C:26]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]([F:37])([F:36])[F:35])=[O:27])[CH2:22][CH2:21]2)=[CH:16][CH:15]=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([NH:13][C:14]2[N:19]=[N:18][C:17]([N:20]3[CH2:21][CH2:22][N:23]([C:26](=[O:27])[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:34]([F:37])([F:36])[F:35])[CH2:24][CH2:25]3)=[CH:16][CH:15]=2)=[O:12])=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004713237285614014,\"rxn_id\":\"ord-50faff58c30844e7bf88838e3c3e521d\",\"index\":505882,\"rxn_smiles\":\"Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1.O=C(O)CCCc1ccccc1>>O=C(CCCc1ccccc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"procedure_details\":\"Following the procedure of Example 1, making variations only as required to use 4-phenylbutyric acid in place of 4-methylpentanoic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (9% yield). 1H NMR (300 MHz, CDCl3) δ 9.13, 8.36, 7.74, 7.62, 7.56, 7.36, 7.28-7.25, 7.19-7.16, 7.05, 4.03-3.98, 3.93-3.88, 3.69-3.60, 3.54-3.52, 3.33-3.31, 2.70, 2.52, 2.06.\",\"reactant_000\":\"O=C(O)CCCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995286762714386,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCc1ccccc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1\",\"rxn_str\":\"[C:1]1([CH2:7][CH2:8][CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][C:14]1[N:19]=[N:18][C:17]([N:20]2[CH2:25][CH2:24][N:23]([C:26]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]([F:37])([F:36])[F:35])=[O:27])[CH2:22][CH2:21]2)=[CH:16][CH:15]=1>>[C:1]1([CH2:7][CH2:8][CH2:9][C:10]([NH:13][C:14]2[N:19]=[N:18][C:17]([N:20]3[CH2:21][CH2:22][N:23]([C:26](=[O:27])[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:34]([F:37])([F:36])[F:35])[CH2:24][CH2:25]3)=[CH:16][CH:15]=2)=[O:12])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005638599395751953,\"rxn_id\":\"ord-b08ef2077e0041f3848ae625041b6fbe\",\"index\":571405,\"rxn_smiles\":\"Nc1ccc2cnn(CCN3CCCC3)c2c1.O=C(O)CCc1ccc(OCc2ccccc2)cc1>>O=C(CCc1ccc(OCc2ccccc2)cc1)Nc1ccc2cnn(CCN3CCCC3)c2c1\",\"procedure_details\":\"According to the procedure for Example 49, 1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-ylamine and 3-(4-benzyloxy-phenyl)-propionic acid were processed to provide the title compound. 1H NMR (500 MHz, DMSO-D6) δ ppm 1.83 (m, 2 H), 2.00 (m, 2 H), 2.66 (t, J=7.64 Hz, 2 H), 2.88 (t, J=7.49 Hz, 2 H), 3.05 (dd, J=10.45, 7.33 Hz, 2 H), 3.53 (m, 2 H), 3.69 (m, 2 H), 4.67 (t, J=6.24 Hz, 2 H), 5.06 (s, 2 H), 6.93 (m, 2 H), 7.07 (m, 1 H), 7.18 (m, 2 H), 7.32 (m, 1 H), 7.40 (m, 4 H), 7.70 (m, 1 H), 8.08 (m, 1 H), 8.28 (s, 1 H), 10.13 (s, 1 H); MS (DCI\\/NH3) m\\/z 469 (M+H)+;\",\"reactant_000\":\"O=C(O)CCc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2cnn(CCN3CCCC3)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994361400604248,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCc1ccc(OCc2ccccc2)cc1)Nc1ccc2cnn(CCN3CCCC3)c2c1\",\"rxn_str\":\"[N:1]1([CH2:6][CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([NH2:17])[CH:15]=3)[CH:10]=[N:9]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34](O)=[O:35])=[CH:28][CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH2:18]([O:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:32][CH2:33][C:34]([NH:17][C:14]2[CH:15]=[C:16]3[C:11]([CH:10]=[N:9][N:8]3[CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:12][CH:13]=2)=[O:35])=[CH:30][CH:31]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005883336067199707,\"rxn_id\":\"ord-71179f252d6141649a50a5f26a9fa6f2\",\"index\":443972,\"rxn_smiles\":\"Nc1ccc2cnn(CCN3CCCC3)c2c1.O=C(O)CCc1ccc(Oc2ccccc2)cc1>>O=C(CCc1ccc(Oc2ccccc2)cc1)Nc1ccc2cnn(CCN3CCCC3)c2c1\",\"procedure_details\":\"According to the procedure for Example 49, 1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-ylamine and 3-(4-phenoxy-phenyl)-propionic acid were processed to provide the title compound. MS (DCI\\/NH3) MS m\\/z 455 (M+H)+; 1H NMR (500 MHz, DMSO-d6) δ ppm 1.84 (m, 2 H), 2.00 (m, 2 H), 2.70 (t, J=7.64 Hz, 2 H), 2.94 (t, J=7.64 Hz, 2 H), 3.05 (m, 2 H), 3.53 (m, 2 H), 3.71 (q, J=5.82 Hz, 2 H), 4.68 (t, J=6.24 Hz, 2 H), 6.95 (m, 4 H), 7.09 (m, 2 H), 7.29 (m, 2 H), 7.36 (m, 2 H), 7.70 (m, 1 H), 8.08 (s, 1 H), 8.28 (s, 1 H), 9.62 (br s, N H).\",\"reactant_000\":\"Nc1ccc2cnn(CCN3CCCC3)c2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(O)CCc1ccc(Oc2ccccc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941166639328003,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCc1ccc(Oc2ccccc2)cc1)Nc1ccc2cnn(CCN3CCCC3)c2c1\",\"rxn_str\":\"[N:1]1([CH2:6][CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([NH2:17])[CH:15]=3)[CH:10]=[N:9]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[O:18]([C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33](O)=[O:34])=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[O:18]([C:25]1[CH:26]=[CH:27][C:28]([CH2:31][CH2:32][C:33]([NH:17][C:14]2[CH:15]=[C:16]3[C:11]([CH:10]=[N:9][N:8]3[CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:12][CH:13]=2)=[O:34])=[CH:29][CH:30]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT TTL T5 UA ALL>>78","id":78},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002769649028778076,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9972303509712219,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0031270384788513184,\"rxn_id\":\"ord-dcc1a5efa86d4d09b08ec14f86ec1748\",\"index\":264188,\"rxn_smiles\":\"Cl.O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12>>Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"procedure_details\":\"A solution of stannous chloride dihydrate (3.7 g, 16 mmol) in 10 ml of conc. hydrochloric acid was added dropwise to a stirred suspension of 2,3-dihydroxy-6-nitrobenzo(f)quinoxaline (1.3 g, 5 mmol) in 8 ml of conc. hydrochloric acid. Then the mixture was stirred at 60-70° C. on an oil bath for 2 h. After cooling on ice, the precipitate was collected, dissolved in boiling water (1 1), filtered while hot, and neutralized to pH 6 with solid sodium hydrogen carbonate. The yellow product was isolated and recrystallized from DMF\\/water, washed with water, ethanol and ether and finally dried at 110 ° C. to give 0.90 g (63%) of pure title compound, m.p. >300° C., IR (KBr): 1690, ? 1640 and 1605 cm-1,1H-NMR (DMSO-d6): 5.8 (broad s, 2H,NH2), 6.63(s,1H, H-5), 7.2-8.7 (m, 4H, ArH), 11.8 (broad s, 2H, 20H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968729615211487,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([OH:19])=[N:4][C:5]2[CH:6]=[C:7]([N+:16]([O-])=O)[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[N:11]=1>Cl>[NH2:16][C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]2[N:11]=[C:2]([OH:1])[C:3]([OH:19])=[N:4][C:5]=2[CH:6]=1\",\"yield_000\":79.2},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.00328141450881958,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9967185854911804,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003656148910522461,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963438510894775,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003899812698364258,\"rxn_id\":\"ord-fc93af0f0d9a40e284c2500298acaf93\",\"index\":573049,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"The crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine was dissolved in THF and reduced using Raney nickel catalyst to yield N4-(3-Chloro-4-fluoro-phenyl)-7-(2,2-difluoro-ethoxy)-quinazoline-4,6-diamine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961001873016357,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C1COCC1.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null}]","literatureScore":1,"label":"UA CF T5 AT ER TTL ALL>>33","id":33},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1150}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1150}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":1150}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":1150}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.68,"id":154,"pathId":1150}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEFNIUDZICAGOU","smiles":"NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1O","intrinsicScore":0.77,"id":33,"pathId":1150}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[N+:21](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[NH2:21])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"T5 ER AT UA TTL ALL>>79","id":79},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"QEYMMOKECZBKAC","smiles":"OC(=O)CCCl","intrinsicScore":0.77,"id":79,"pathId":1150}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"BHEIYHLWRREISX","smiles":"OC1=C(NC(=O)CCCl)C=C2C(NC3=CC=C(F)C(Cl)=C3)=NC=NC2=C1","intrinsicScore":0.14,"id":78,"pathId":1150}],"RXN":"[cH:19]1[cH:20][c:21]([c:22]([cH:23][c:18]1[NH:17][c:16]2[c:10]3[cH:9][c:8]([c:7]([cH:12][c:11]3[n:13][cH:14][n:15]2)[OH:6])[NH2:26])[Cl:24])[F:25].[CH2:2]([CH2:1][Cl:5])[C:3](=[O:4])O>>[cH:19]1[cH:20][c:21]([c:22]([cH:23][c:18]1[NH:17][c:16]2[c:10]3[cH:9][c:8]([c:7]([cH:12][c:11]3[n:13][cH:14][n:15]2)[OH:6])[NH:26][C:3](=[O:4])[CH2:2][CH2:1][Cl:5])[Cl:24])[F:25];2.1.2;Carboxylic"},{"depth":2,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.14,"id":43,"pathId":1150}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1150}],"RXN":"[cH:9]1[cH:10][c:11]([c:12]([cH:14][c:8]1[NH:7][c:6]2[c:5]3[cH:4][c:3]([c:2]([cH:20][c:19]3[n:18][cH:17][n:16]2)[OH:1])[NH:21][C:22](=[O:26])[CH2:23][CH2:24][Cl:25])[Cl:13])[F:15].[CH2:28]1[CH2:27][O:35][CH2:34][CH2:33][N:29]1[CH2:30][CH2:31][CH2:32]O>N(C(=O)OCC)=NC(=O)OCC.OC.ClCCl.C1=CC(=CC=C1)P(C2=CC=CC=C2)C3=CC=CC=C3>[cH:9]1[cH:10][c:11]([c:12]([cH:14][c:8]1[NH:7][c:6]2[c:5]3[cH:4][c:3]([c:2]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:1][CH2:32][CH2:31][CH2:30][N:29]4[CH2:28][CH2:27][O:35][CH2:34][CH2:33]4)[NH:21][C:22](=[O:26])[CH2:23][CH2:24][Cl:25])[Cl:13])[F:15];1.7.7;Mitsunobu"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1150}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-7.782","depth":0,"reaction":{"label":">>0","id":0,"pathId":222},"children":[{"depth":1,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002493739128112793,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975062608718872,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.00285494327545166,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971450567245483,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.002886652946472168,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971133470535278,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003403782844543457,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9965962171554565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003649115562438965,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.996350884437561,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"LR ALL>>28","id":28},"children":[{"depth":3,"reaction":{"scalabilityModelScore":5.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004645109176635742,\"rxn_id\":\"ord-75359f89be174903b9bf817cd5092295\",\"index\":125243,\"rxn_smiles\":\"C1CCOC1.CCOC(=O)N=NC(=O)OCC.COC(=O)c1cc(OCC=C(Cl)Cl)cc(Cl)c1O.OCCCOc1ccc(C(F)(F)F)cn1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COC(=O)c1cc(OCC=C(Cl)Cl)cc(Cl)c1OCCCOc1ccc(C(F)(F)F)cn1\",\"procedure_details\":\"Under an atmosphere of protective gas, 1.85 g of methyl 3-chloro-5-(3,3-dichloroprop-2-enyloxy)-2-hydroxybenzoate, 1.3 g of 3-(5-trifluoromethylpyrid-2-yloxy)-propan-1-ol and 1.64 g of triphenylphosphine were dissolved in 50 ml of dry tetrahydrofuran (THF). With ice-bath cooling, 1.09 g of diethyl azodicarboxylate were added dropwise. After about 30 minutes, the ice-bath was removed, and the mixture was stirred at room temperature for 15 hours. The mixture was then concentrated under reduced pressure and the residue was taken up in a mixture of ethyl acetate and water. After shaking, the organic phase was isolated, dried and concentrated under reduced pressure. The crude product was purified chromatographically. Yield: 1.79 g (59%)\",\"reactant_000\":\"OCCCOc1ccc(C(F)(F)F)cn1\",\"reactant_002\":null,\"reactant_001\":\"COC(=O)c1cc(OCC=C(Cl)Cl)cc(Cl)c1O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9953548908233643,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COC(=O)c1cc(OCC=C(Cl)Cl)cc(Cl)c1OCCCOc1ccc(C(F)(F)F)cn1\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]([OH:18])=[C:4]([CH:9]=[C:10]([O:12][CH2:13][CH:14]=[C:15]([Cl:17])[Cl:16])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:19][C:20]([F:33])([F:32])[C:21]1[CH:22]=[CH:23][C:24]([O:27][CH2:28][CH2:29][CH2:30]O)=[N:25][CH:26]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[Cl:1][C:2]1[C:3]([O:18][CH2:30][CH2:29][CH2:28][O:27][C:24]2[CH:23]=[CH:22][C:21]([C:20]([F:33])([F:19])[F:32])=[CH:26][N:25]=2)=[C:4]([CH:9]=[C:10]([O:12][CH2:13][CH:14]=[C:15]([Cl:16])[Cl:17])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0056236982345581055,\"rxn_id\":\"ord-5110d57e891a4de49f8c2e81d8f9fd03\",\"index\":533282,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Cl)ncnc2cc1O.ClCCl.OCCCN1CCN(CCF)CC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1\",\"procedure_details\":\"A suspension of 4-chloro-7-hydroxy-6-methoxyquinazoline (202 mg, 0.96 mmol), (prepared as described for the starting material in Example 4), in methylene chloride (10 ml) was treated with triphenylphosphine (352 mg, 1.35 mmol), 3-[4-(2-fluoroethyl)piperazin-1-yl)propan-1-ol (200 mg, 1.06 mmol), (prepared as described for the starting material in Example 27), and diisopropyl azodicarboxylate (226 mg, 1.15 mmol) and the mixture stirred at ambient temperature for 2 hours. The crude reaction mixture was loaded onto a silica column and eluted using methylene chloride\\/methanol (95\\/5). The relevant fractions were combined and evaporated under vacuum to give 4-chloro-7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxyquinazoline (208 mg, 57%) as a white solid.\",\"reactant_000\":\"OCCCN1CCN(CCF)CC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Cl)ncnc2cc1O\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9943763017654419,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][CH2:45]O)[CH2:39][CH2:38]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:45][CH2:44][CH2:43][N:40]3[CH2:39][CH2:38][N:37]([CH2:36][CH2:35][F:34])[CH2:42][CH2:41]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1\",\"yield_000\":56.6},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005681931972503662,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9943180680274963,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005808234214782715,\"rxn_id\":\"ord-4b054211a383477dbfd56ba4b81f1d7f\",\"index\":309238,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.COc1ccccc1N(C)C(=O)c1cc(-c2cnc(C(F)(F)F)cc2C#N)c(Cl)cc1O.OCCCc1cnoc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1ccccc1N(C)C(=O)c1cc(-c2cnc(C(F)(F)F)cc2C#N)c(Cl)cc1OCCCc1cnoc1\",\"procedure_details\":\"To a solution of 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-hydroxy-N-(2-methoxy-phenyl)-N-methyl-benzamide (30 mg, 0.065 mmol) in THF (700 μL), 3-isoxazol-4-yl-propan-1-ol (9 mg, 0.071 mmol), triphenylphosphine (26 mg, 0.089 mmol) and DIAD (20 μL, 0.098 mmol) were added. The mixture was stirred at rt overnight, concentrated, diluted with 1 mL MeOH and purified by prep HPLC to give 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-(3-isoxazol-4-yl-propoxy)-N-(2-methoxyphenyl)-N-methyl-benzamide 46-1. MS: 571.2 (M+H)+, tR=6.12 min (method 3).\",\"reactant_000\":\"OCCCc1cnoc1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccccc1N(C)C(=O)c1cc(-c2cnc(C(F)(F)F)cc2C#N)c(Cl)cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9941917657852173,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1ccccc1N(C)C(=O)c1cc(-c2cnc(C(F)(F)F)cc2C#N)c(Cl)cc1OCCCc1cnoc1\",\"rxn_str\":\"[Cl:1][C:2]1[C:19]([C:20]2[CH:21]=[N:22][C:23]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:25]=2[C:26]#[N:27])=[CH:18][C:5]([C:6]([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[CH3:9])=[O:7])=[C:4]([OH:32])[CH:3]=1.[O:33]1[CH:37]=[C:36]([CH2:38][CH2:39][CH2:40]O)[CH:35]=[N:34]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:19]([C:20]2[CH:21]=[N:22][C:23]([C:28]([F:29])([F:30])[F:31])=[CH:24][C:25]=2[C:26]#[N:27])=[CH:18][C:5]([C:6]([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[CH3:9])=[O:7])=[C:4]([O:32][CH2:40][CH2:39][CH2:38][C:36]2[CH:35]=[N:34][O:33][CH:37]=2)[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006024599075317383,\"rxn_id\":\"ord-0a0c59e5886c4ff29169d70a1350d8c8\",\"index\":413811,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.COC(=O)C1(NC(=O)c2ccc(OC)c(O)c2)CCCCCC1.OCCc1cc(Cl)ccc1F.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COC(=O)C1(NC(=O)c2ccc(OC)c(OCCc3cc(Cl)ccc3F)c2)CCCCCC1\",\"procedure_details\":\"The compound of step 2 (80 mg, 0.249 mmol) and triphenylphosphine (98 mg, 0.374 mmol) were dissolved in THF. 2-(5-Chloro-2-fluoro-phenyl)-ethanol (48 mg, 0.274 mmol) and DIAD (80.3 mg, 0.374 mmol) were added and the mixture was stirred at room temperature for 2 h. The volatiles were evaporated in vacuo and the residue was purified by preparative RP HPLC (water\\/ACN gradient) to give 85 mg of the title compound.\",\"reactant_000\":\"COC(=O)C1(NC(=O)c2ccc(OC)c(O)c2)CCCCCC1\",\"reactant_002\":null,\"reactant_001\":\"OCCc1cc(Cl)ccc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9939754009246826,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COC(=O)C1(NC(=O)c2ccc(OC)c(OCCc3cc(Cl)ccc3F)c2)CCCCCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]([C:5]1([NH:12][C:13](=[O:23])[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([OH:22])[CH:15]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:43][C:44]1[CH:45]=[CH:46][C:47]([F:53])=[C:48]([CH2:50][CH2:51]O)[CH:49]=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[CH3:1][O:2][C:3]([C:5]1([NH:12][C:13](=[O:23])[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH2:51][CH2:50][C:48]3[CH:49]=[C:44]([Cl:43])[CH:45]=[CH:46][C:47]=3[F:53])[CH:15]=2)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1)=[O:4]\",\"yield_000\":71.4}]","literatureScore":1,"label":"T5 AT ER UA ALL>>228","id":228},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.004299342632293701,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9957006573677063,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.004652976989746094,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9953470230102539,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00585097074508667,\"rxn_id\":\"ord-51bfffc1cc3f48bfba7729fb1fa37a5a\",\"index\":347091,\"rxn_smiles\":\"BrBr.COC(=O)c1sc(-c2ccccc2)cc1O>>COC(=O)c1sc(-c2ccccc2)c(Br)c1O\",\"procedure_details\":\"Prepared by the method described in Example 4 from methyl 3-hydroxy-5-phenyl-2-thiophenecarboxylate (5.0 g, 21 mmoles) and bromine (3.4 g, 21 mmoles). Recrystallization from methanol gave the product (4.0 g); mp 85°-87° C.\",\"reactant_000\":\"COC(=O)c1sc(-c2ccccc2)cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941490292549133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)c1sc(-c2ccccc2)c(Br)c1O\",\"rxn_str\":\"[OH:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14].[Br:17]Br>>[OH:1][C:2]1[C:6]([Br:17])=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14]\",\"yield_000\":60.8},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.006023406982421875,\"rxn_id\":\"ord-cec279efa24d480ba329f30936792dee\",\"index\":224777,\"rxn_smiles\":\"BrBr.CC(=O)O.O=C(O)c1cc2ccccc2cc1O>>O=C(O)c1cc2ccccc2c(Br)c1O\",\"procedure_details\":\"3-Hydroxynaphthalene-2-carboxylic acid (3.0 g, 15.9 mmol) was suspended in acetic acid (40 mL) and with vigorous stirring a solution of bromine (817 μL, 15.9 mmol) in acetic acid (10 mL) was added drop wise during 30 minutes. The suspension was stirred at room temperature for 1 hour, filtered and washed with water. Drying in vacuo afforded 3.74 g (88%) of 4-bromo-3-hydroxynaphthalene-2-carboxylic acid as a solid.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"O=C(O)c1cc2ccccc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9939765930175781,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C(O)c1cc2ccccc2c(Br)c1O\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([C:12]([OH:14])=[O:13])=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[Br:15]Br>C(O)(=O)C>[Br:15][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:12]([OH:14])=[O:13])[C:2]=1[OH:1]\",\"yield_000\":88.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.006250619888305664,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9937493801116943,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null}]","literatureScore":1,"label":"UA T5 AT ER TTL ALL>>527","id":527},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":222}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":222}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":222}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":222}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.58,"id":154,"pathId":222}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":5,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.58,"id":522,"pathId":222}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RRIGCTITGHGCKU","smiles":"OC1=C(Br)C2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.16,"id":527,"pathId":222}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[Br:24]Br>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([c:21]([c:7]3[n:8][cH:9][n:10]2)[Br:24])[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];10.1.1;Bromination"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.33,"id":43,"pathId":222}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"JWFJQOCJPWGBQR","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C(Br)=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1","intrinsicScore":0.71,"id":228,"pathId":222}],"RXN":"[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[OH:24])[N+:18](=[O:19])[O-:20])[Cl:10])[F:9].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25]O>O1CCCC1.O=C(/N=N/C(OCC)=O)OCC.C1=CC=C(P(C2=CC=CC=C2)C3=CC=CC=C3)C=C1>[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9];1.7.7;Mitsunobu"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":222}],"RXN":"[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:26])[F:30]>>[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:26])[F:30];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":222}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":222}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":222}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.786","depth":0,"reaction":{"label":">>0","id":0,"pathId":288},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":288}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":288}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":288}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":288}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":288}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":288}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":288}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":288}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":288}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":288}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":288}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":288}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.801","depth":0,"reaction":{"label":">>0","id":0,"pathId":1853},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.003749549388885498,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962504506111145,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"CC(C)(C)O\",\"distance\":0.00415647029876709,\"rxn_id\":\"ord-5510c71cc19244ccb4d87f14f34e8de5\",\"index\":424079,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"procedure_details\":\"To a solution of 4-chloro-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine (40 mg, 0.15 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 1 ml) was added 3-chloro-4-fluoroaniline (22 mg, 0.15 mmol). The mixture was heated at 90° C. for 2 days. After cooling down to room temperature, the solvents were removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 100:1) to yield the title compound as a white solid (28 mg, 50%).\",\"reactant_000\":\"Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9958435297012329,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[CH:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":49.9},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.004578828811645508,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9954211711883545,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004691362380981445,\"rxn_id\":\"ord-1706282351e44a6a96c8cda1fd077e00\",\"index\":312255,\"rxn_smiles\":\"CN(C)C=O.COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Nc1c(F)cc(Cl)cc1F.[H-].[Na+]>>COc1cc2c(Nc3c(F)cc(Cl)cc3F)ncnc2cc1OCC1CCN(C)CC1\",\"procedure_details\":\"Using an analogous procedure to that described in Example 4, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (246 mg, 0.764 mmol), (prepared as described for the starting material in Example 2c), was reacted with 4-chloro-2,6-difluoroaniline (250 mg, 1.53 mmol), (see WO 97\\/30035 Example 15), in DMF (9 ml) and in the presence of sodium hydride (60%, 76.5 mg, 1.9 mmol) to give 4-(4-chloro-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (210 mg, 61%).\",\"reactant_000\":\"Nc1c(F)cc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9953086376190186,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3c(F)cc(Cl)cc3F)ncnc2cc1OCC1CCN(C)CC1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH2:28])=[C:26]([F:32])[CH:25]=1.[H-].[Na+]>CN(C=O)C>[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH:28][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[C:26]([F:32])[CH:25]=1\",\"yield_000\":61.2},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.005193650722503662,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9948063492774963,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004627108573913574,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9953728914260864,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.005324959754943848,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9946750402450562,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0059626102447509766,\"rxn_id\":\"ord-46b7aabe19fa4743a938b1aaa2a0a56d\",\"index\":662518,\"rxn_smiles\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3F)n2)c1.OCCCF>>CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCCCF)n2)c1\",\"procedure_details\":\"Starting with 4-(2,4-difluorophenyl)-N-{3-[(methylsulfonyl)methyl]phenyl}-1,3,5-triazin-2-amine (75 mg; 0.197 mmol), intermediate 42.1, and 3-fluoropropan-1-ol (59 mg; 0.736 mmol), example 54 was prepared analogously to the procedure for the preparation of example 42.\",\"reactant_000\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3F)n2)c1\",\"reactant_002\":null,\"reactant_001\":\"OCCCF\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994037389755249,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCCCF)n2)c1\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:17]=2)[N:10]=1.[F:27][CH2:28][CH2:29][CH2:30][OH:31]>>[F:8][C:6]1[CH:5]=[CH:4][C:3]([C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:17]=3)[N:10]=2)=[C:2]([O:31][CH2:30][CH2:29][CH2:28][F:27])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006279468536376953,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.993720531463623,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006436705589294434,\"rxn_id\":\"ord-855ef139e6ed4c179e58d194cc378f0b\",\"index\":33547,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.O[C@@H]1CCOC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@@H]1CCOC1\",\"procedure_details\":\"13.80 g of potassium tert-butoxide are added batchwise to a solution of 10.80 g of (R)-3-hydroxytetrahydrofuran in 100 ml of N,N-dimethylformamide while cooling with an ice bath. The reaction mixture is stirred for about one hour, then 10.40 g of 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-fluoroquinazoline are added batchwise. The cooling bath is then removed and the deep red reaction mixture is stirred for two hours at ambient temperature. For working up the reaction mixture is poured onto about 500 ml of water and neutralized with 2 N hydrochloric acid. The yellowish precipitate formed is suction filtered and dried at 70° C. in a circulating air drier. Yield: 12.80 g; melting point: 244° C.; mass spectrum (ESI−): m\\/z=403, 405 [M−H]−.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O[C@@H]1CCOC1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9935632944107056,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@@H]1CCOC1\",\"rxn_str\":\"CC(C)([O-])C.[K+].[OH:7][C@@H:8]1[CH2:12][CH2:11][O:10][CH2:9]1.[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20].Cl>CN(C)C=O.O>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:7][C@@H:8]4[CH2:12][CH2:11][O:10][CH2:9]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA ER ALL>>495","id":495},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":1853}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":1853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.098,"id":460,"pathId":1853}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.33,"id":92,"pathId":1853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOWKNWPFXSSYBZ","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2Cl","intrinsicScore":0.26,"id":495,"pathId":1853}],"RXN":"[cH:5]1[c:6]2[c:12]([cH:13][c:14]([c:4]1[N+:2](=[O:1])[O-:3])F)[n:11][cH:10][n:9][c:7]2[Cl:8].[CH2:17]([CH2:16][OH:15])[CH2:18][Cl:19]>>[cH:5]1[c:6]2[c:12]([cH:13][c:14]([c:4]1[N+:2](=[O:1])[O-:3])[O:15][CH2:16][CH2:17][CH2:18][Cl:19])[n:11][cH:10][n:9][c:7]2[Cl:8];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.26,"id":19,"pathId":1853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1853}],"RXN":"[cH:22]1[cH:23][c:24]([c:19]([cH:20][c:21]1[NH2:26])[Cl:27])[F:25].[cH:4]1[c:3]2[c:2]([cH:12][c:6]([c:5]1[N+:13](=[O:14])[O-:15])[O:7][CH2:8][CH2:9][CH2:10][Cl:11])[n:1][cH:18][n:17][c:16]2Cl>>[cH:22]1[cH:23][c:24]([c:19]([cH:20][c:21]1[NH:26][c:16]2[c:3]3[cH:4][c:5]([c:6]([cH:12][c:2]3[n:1][cH:18][n:17]2)[O:7][CH2:8][CH2:9][CH2:10][Cl:11])[N+:13](=[O:14])[O-:15])[Cl:27])[F:25];1.3.7;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1853}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1853}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1853}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1853}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-7.836","depth":0,"reaction":{"label":">>0","id":0,"pathId":2019},"children":[{"depth":1,"reaction":{"scalabilityModelScore":5.2,"literature":"[{\"solvent_000\":\"ClP(Cl)Cl\",\"solvent_001\":\"ClC(Cl)Cl\",\"distance\":0.03222155570983887,\"rxn_id\":\"ord-4ee3d8d301824f80b57afcbb6894ed3d\",\"index\":186003,\"rxn_smiles\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC.ClC(Cl)Cl.ClP(Cl)Cl>>COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"procedure_details\":\"A solution of N-oxide 3 (10 mM) and phosphorus trichloride (30 mM) in anhydrous chloroform (100 ml) was refluxed for 7 h. Solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulphate and then evaporated under reduced pressure. The residue was recrystallized from isopropanol to provide the title dimethyl quinoline-2,3-dicarboxylate 7 as an off white (or light yellow) powder.\",\"reactant_000\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9677784442901611,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"rxn_str\":\"[N+:1]1([O-])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16].P(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1=CCCCC1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.03826326131820679,\"rxn_id\":\"ord-e79e74c481414470aec1b7e2b799dffb\",\"index\":735026,\"rxn_smiles\":\"C1=CCCCC1.CC(C)O.COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1.[Pd]>>COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"procedure_details\":\"A mixture of 7-({2-[(4-methoxybenzyl)amino]-1-oxidopyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (21.1 g, 0.0502 mol), cyclohexene (100 mL, 0.9 mol) and Pd (10% on Carbon, 4.5 g) in isopropyl alcohol (400 mL, 5 mol) was heated at 85° C. overnight. Additional catalyst (2.5 g) and cyclohexene (30 mL) were added. The mixture was heated at 90° C. overnight and then filtered. The filtrate was concentrated to give 7-({2-[(4-methoxybenzyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid which was used in the next step without purification. LCMS ES+ 405.7\",\"reactant_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9617367386817932,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":85.0,\"product_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N+:10]=2[O-])=[CH:5][CH:4]=1.C(O)(C)C>[Pd].C1CCCCC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[CH:30][CH:31]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.03870534896850586,\"rxn_id\":\"ord-2fc2b37b70194a0cb07bb83eba1a43cc\",\"index\":771709,\"rxn_smiles\":\"CC(=O)O.CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)[n+]([O-])c2)c2cc(C)oc2c1.[Fe]>>CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)nc2)c2cc(C)oc2c1\",\"procedure_details\":\"To a stirred solution of ethyl 4-({6-[(dimethylamino)carbonyl]-1-oxidopyridin-3-yl}oxy)-2-methyl-1-benzofuran-6-carboxylate (176 mg, 0.457 mmol) in 15 mL of acetic acid, was added powdered Fe while keeping the temperature at 70° C. for 2 hrs. LC-MS showed that the reaction was complete. The reaction was cooled to room temperature, and the insoluble material was filtered. The mother liquor was diluted with EtOAc, washed with NaHCO3, brine, and dried over Na2SO4, and concentrated. The crude product was introduced into a silica gel column and eluted with MeOH\\/CHCl3 (2\\/98 to 5\\/95) to provide the product (135 mg, 85% yield) as colorless oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.40 (t, J=7.16 Hz, 3H) 2.47 (s, 3 H) 3.15 (d, 6 H) 4.39 (q, J=7.03 Hz, 2 H) 6.25 (s, 1 H) 7.30 (d, J=2.45 Hz, 1 H) 7.55-7.64 (m, 1 H) 7.64-7.76 (m, 1 H) 8.00 (s, 1 H) 8.38 (s, 1 H); LC-MS (ESI)+m\\/z=369.00 (M+H)+.\",\"reactant_000\":\"CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)[n+]([O-])c2)c2cc(C)oc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9612946510314941,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)nc2)c2cc(C)oc2c1\",\"rxn_str\":\"[CH3:1][N:2]([CH3:28])[C:3]([C:5]1[N+:10]([O-])=[CH:9][C:8]([O:12][C:13]2[C:18]3[CH:19]=[C:20]([CH3:22])[O:21][C:17]=3[CH:16]=[C:15]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:14]=2)=[CH:7][CH:6]=1)=[O:4]>C(O)(=O)C.[Fe]>[CH3:28][N:2]([CH3:1])[C:3]([C:5]1[N:10]=[CH:9][C:8]([O:12][C:13]2[C:18]3[CH:19]=[C:20]([CH3:22])[O:21][C:17]=3[CH:16]=[C:15]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:14]=2)=[CH:7][CH:6]=1)=[O:4]\",\"yield_000\":80.2},{\"solvent_000\":\"CCO\",\"solvent_001\":\"O\",\"distance\":0.039771080017089844,\"rxn_id\":\"ord-ac830d54b7724a8b93da7678034827fa\",\"index\":571122,\"rxn_smiles\":\"CCO.Cc1cc(Br)c2nc(O)c[n+]([O-])c2c1.O.O=S([O-])S(=O)[O-].[Na+].[Na+]>>Cc1cc(Br)c2nc(O)cnc2c1\",\"procedure_details\":\"The title compound of Step C (25 g, 98 mmol) and sodium dithionite (38 g, 220 mmol) were suspended in a mixture of ethanol (1000 mL) and water (200 mL) at room temperature. After 1 h, most of the solvent was removed under reduced pressure. The residue was diluted with water and acidified with hydrochloric acid. Insolubles were removed by filtration. The filtrate was extracted twice with methylene chloride. The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure to afford the title compound of Step D as a tan\\/yellow solid (15.29 g, 65%). 1H NMR (CDCl3): δ2.37 (s,3H), 7.5 (d,2H), 8.15 (s, 1H), 9.8 (br s, 1H).\",\"reactant_000\":\"Cc1cc(Br)c2nc(O)c[n+]([O-])c2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9602289199829102,\"agent_000\":\"O=S([O-])S(=O)[O-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Br)c2nc(O)cnc2c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([OH:12])[CH:8]=[N+:7]2[O-].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([OH:12])[CH:8]=[N:7]2\",\"yield_000\":65.3},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCOC(C)=O\",\"distance\":0.0405157208442688,\"rxn_id\":\"ord-bcf39c7a08824c81bf28cf3712936702\",\"index\":724869,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)OC(=O)NCCN(C(=O)OC(C)(C)C)c1ccc(CC(=O)O)c[n+]1[O-].CCOC(C)=O.[Cl-].[NH4+].[Zn]>>CC(C)(C)OC(=O)NCCN(C(=O)OC(C)(C)C)c1ccc(CC(=O)O)cn1\",\"procedure_details\":\"To 2-(tert-butoxycarbonyl(2-(tert-butoxycarbonylamino)ethyl)amino)-5-(carboxymethyl)pyridine 1-oxide (0.78 g) in a mixture of THF (10 mL) and sat. NH4Cl (10 mL) was added Zinc dust (0.65 g). The reaction mixture was stirred at room temperature for overnight. EtOAc was then added and washed with water. The organic phase was dried and concentrated to afford the desired product (0.5 g).\",\"reactant_000\":\"CC(C)(C)OC(=O)NCCN(C(=O)OC(C)(C)C)c1ccc(CC(=O)O)c[n+]1[O-]\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9594842791557312,\"agent_000\":\"[Cl-]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[Zn]\",\"temperature\":25.0,\"product_000\":\"CC(C)(C)OC(=O)NCCN(C(=O)OC(C)(C)C)c1ccc(CC(=O)O)cn1\",\"rxn_str\":\"[C:1]([O:5][C:6]([N:8]([CH2:20][CH2:21][NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:11][N+:10]=1[O-])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH4+].[Cl-].CCOC(C)=O>C1COCC1.[Zn]>[C:1]([O:5][C:6]([N:8]([CH2:20][CH2:21][NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:9]1[N:10]=[CH:11][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:13][CH:14]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]\",\"yield_000\":66.7}]","literatureScore":0.97,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":6.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.06608951091766357,\"rxn_id\":\"ord-9b239ee410874131801acfbc5a613f8b\",\"index\":208806,\"rxn_smiles\":\"CC=CC(=O)Cl.ClCCl.NC(=O)c1cc(Cl)ccc1N>>C=C(C)C(=O)Nc1ccc(Cl)cc1C(N)=O\",\"procedure_details\":\"2-Amino-5-chloro-benzamide (2.5 mmoL), a literature known compound, was treated with TEA (3.0 mmoL) followed by methylacryl chloride (2.5 mmoL) in DCM at 0° C. The reaction was slowly warmed to room temperature and kept for another 2 h. The reaction mixture was then partitioned between DCM and water. The organic layer was washed with sat. Na2CO3, brine, dried over anhydrous Na2SO4, filtered, concentrated and purified by silica gel column chromatography to afford the title compound as a white solid.\",\"reactant_000\":\"CC=CC(=O)Cl\",\"reactant_002\":\"ClCCl\",\"reactant_001\":\"NC(=O)c1cc(Cl)ccc1N\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9339104890823364,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=C(C)C(=O)Nc1ccc(Cl)cc1C(N)=O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].C[CH:13]=[CH:14][C:15](Cl)=[O:16].[CH2:18](Cl)Cl>>[Cl:11][C:8]1[CH:9]=[CH:10][C:2]([NH:1][C:15](=[O:16])[C:14]([CH3:18])=[CH2:13])=[C:3]([CH:7]=1)[C:4]([NH2:6])=[O:5]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.07079339027404785,\"rxn_id\":\"ord-60d9061fa3f543a2a9376bc8387bb8c1\",\"index\":66111,\"rxn_smiles\":\"C=C(Cl)C(=O)O.CCN(CC)CC.COC(=O)[C@@H](N)Cc1c[nH]cn1.Cl.Cl.ClCCl>>C=CC(=O)N[C@@H](Cc1c[nH]cn1)C(=O)OC\",\"procedure_details\":\"After chloroacrylic acid (1.6 ml, 20 mmol) was dropped, with ice cooling, into a solution of histidine methyl ester dihydrochloride (6.05 g, 25 mmol) and triethylamine (14 mL, 100 mmol) in methylene chloride (200 mL), the same operation as in the synthesis of N(α)-acryloyl-N(π)-methyl-L-histidine methyl ester was conducted to give N(α)-acryloyl-L-histidine methyl ester (2.0 g, 36%) as an oily product.\",\"reactant_000\":\"COC(=O)[C@@H](N)Cc1c[nH]cn1\",\"reactant_002\":null,\"reactant_001\":\"C=C(Cl)C(=O)O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9292066097259521,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)N[C@@H](Cc1c[nH]cn1)C(=O)OC\",\"rxn_str\":\"Cl[C:2](=[CH2:6])[C:3](O)=[O:4].Cl.Cl.[CH3:9][O:10][C:11](=[O:20])[C@H:12]([CH2:14][C:15]1[N:19]=[CH:18][NH:17][CH:16]=1)[NH2:13].C(N(CC)CC)C>C(Cl)Cl>[CH3:9][O:10][C:11](=[O:20])[C@H:12]([CH2:14][C:15]1[N:19]=[CH:18][NH:17][CH:16]=1)[NH:13][C:3](=[O:4])[CH:2]=[CH2:6]\",\"yield_000\":44.8},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN1CCCC1=O\",\"distance\":0.07334160804748535,\"rxn_id\":\"ord-f206d1ea171946c7839ab8165e95848b\",\"index\":522923,\"rxn_smiles\":\"CN(C)C\\/C=C\\/C(=O)Cl.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1>>CC=CC(=O)Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1\",\"procedure_details\":\"To a stirred solution of N2-(6-(4-phenoxyphenoxy)pyrimidin-4-yl)pyridine-2,6-diamine (0.65 g, 1.75 mmol) in NMP (10 mL) was added dimethylaminocrotonyl chloride (1.026 g, 7 mmol) at 0° C. The reaction mixture was allowed to come to room temperature and kept at it for 1 h. It was diluted with dichloromethane (10 mL), was washed with NaHCO3 solution (2 mL) and water (2 mL), and dried over Na2SO4. The dichloromethane solution was filtered and was concentrated under reduced pressure to give a residue that was purified by column chromatography (SiO2, 60-120, chloroform\\/methanol, 9\\/1) to give (E)-4-dimethylamino)-N-(6-(6-(4-phenoxyphenoxy)pyrimidin-4-ylamino)pyridin-2-yl)but-2-enamide (I-82) as an off white solid. 1H NMR (DMSO-d6) δ ppm: 2.19 (s, 6H), 3.08 (d, J=5.52 Hz, 2H), 6.50 (d, J=15.4 Hz, 1H), 6.77 (td, J=5.92 & 15.4 Hz, 1H), 7.00-7.07 (m, 5H), 7.15 (t, J=7.36 Hz, 1H), 7.21 (dd, J=2.2 & 8.92 Hz, 2H), 7.41 (t, J=7.52 Hz, 2H), 7.68 (t, J=7.96 Hz, 1H), 7.77 (d, J=7.96 Hz, 1H), 7.95 (s, 1H), 8.35 (s, 1H), 10.20 (s, 1H), 10.40 (s, 1H); LCMS: m\\/e 483 (M+1).\",\"reactant_000\":\"Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1\",\"reactant_002\":null,\"reactant_001\":\"CN(C)C\\/C=C\\/C(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9266583919525146,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC=CC(=O)Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1\",\"rxn_str\":\"[O:1]([C:8]1[CH:28]=[CH:27][C:11]([O:12][C:13]2[N:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([NH2:26])[N:21]=3)[CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN([CH2:32]\\/[CH:33]=[CH:34]\\/[C:35](Cl)=[O:36])C>CN1C(=O)CCC1.ClCCl>[O:1]([C:8]1[CH:28]=[CH:27][C:11]([O:12][C:13]2[N:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[N:21]=[C:22]([NH:26][C:35](=[O:36])[CH:34]=[CH:33][CH3:32])[CH:23]=[CH:24][CH:25]=3)[CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.07634156942367554,\"rxn_id\":\"ord-37af189c9f074f43975d0a666e77eed4\",\"index\":74200,\"rxn_smiles\":\"COC(=O)C1CC2C=CC1O2.Cl.Nc1ccccc1.O>>C=CC(=O)Nc1ccccc1\",\"procedure_details\":\"7.2 parts 30% methanolic Na-methylate solution are added to 46.5 parts aniline. 77 parts 2-carbomethoxy-7-oxabicyclo(2,2,1)hept-5-ene are added drop-wise at 40° C. The reaction medium is then stirred for 15 hours at this temperature and neutralised with 4 parts concentrated hydrochloric acid. 50 parts water are added, and the organic phase separated off. The organic phase is reduced in a rotary evaporator at a bath temperature of 90° C. and under a vacuum of 20 Torr. The residue is heated in a vacuum of 20 Torr to 110° to 120° C. (bath temperature 140° C.). On conclusion of the furane separation, the sedimentation temperature increases and the product distills over. 27.5 parts N-phenylacrylamide with a boiling point of 135° C. at 0.4 Torr are obtained. The product recrystallised from the acetonitrile at -20° C. has a melting point of 114° to 115° C.\",\"reactant_000\":\"Nc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"COC(=O)C1CC2C=CC1O2\",\"rxn_time\":15.0,\"reactant_003\":null,\"similarity\":0.9236584305763245,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"C=CC(=O)Nc1ccccc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:8]([CH:12]1CC2O[CH:13]1C=C2)(OC)=[O:9].Cl>O>[C:2]1([NH:1][C:8](=[O:9])[CH:12]=[CH2:13])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CC#N\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.08093816041946411,\"rxn_id\":\"ord-5f64f7331f114d09a892ddee5f9bd4b8\",\"index\":490819,\"rxn_smiles\":\"CC#N.CC(C)\\/C=C\\/C(=O)O.CCN(CC)CC.CN(C)C(On1nnc2ccccc21)=[N+](C)C.Cc1cc(NCCN)c2ccccc2n1.F[P-](F)(F)(F)(F)F>>C\\/C=C\\/C(=O)NCCNc1cc(C)nc2ccccc12\",\"procedure_details\":\"(E)-4-Methylpent-2-enoic acid (190 mg, 1.3 mmol) was mixed together with HBTU (470 mg, 1.3 mmol) and N-(2-methyl-4-quinolyl)ethane-1,2-diamine (250 mg, 1.2 mmol) in acetonitrile (5 ml). Triethylamine (1 mll) was added with stirring at 0° C. over 15 minutes and the resulting mixture was stirred at room temperature overnight. The volatiles were removed under reduced pressure, the residue was dissolved in DCM and washed with a saturated solution of sodium bicarbonate. The combined aqueous solutions were extracted three times with DCM. The organic layers were combined, dried over sodium sulfate, the solvent was removed under reduced pressure to give 245 mg of a yellow solid (0.82 mmol, 66%). MS (APCI) m\\/z=298.2 [M+1]+.\",\"reactant_000\":\"Cc1cc(NCCN)c2ccccc2n1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)\\/C=C\\/C(=O)O\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9190618395805359,\"agent_000\":\"CN(C)C(On1nnc2ccccc21)=[N+](C)C\",\"agent_001\":\"F[P-](F)(F)(F)(F)F\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C\\/C=C\\/C(=O)NCCNc1cc(C)nc2ccccc12\",\"rxn_str\":\"C[CH:2](C)\\/[CH:3]=[CH:4]\\/[C:5](O)=[O:6].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:33][C:34]1[CH:43]=[C:42]([NH:44][CH2:45][CH2:46][NH2:47])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:35]=1.C(N(CC)CC)C>C(#N)C>[CH3:33][C:34]1[CH:43]=[C:42]([NH:44][CH2:45][CH2:46][NH:47][C:5](=[O:6])\\/[CH:4]=[CH:3]\\/[CH3:2])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:35]=1\",\"yield_000\":68.3}]","literatureScore":0.93,"label":"UA TTL ALL>>40","id":40},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.014116823673248291,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9858831763267517,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.016109049320220947,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.983890950679779,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01629471778869629,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9837052822113037,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.017170846462249756,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9828291535377502,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.018261253833770752,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9817387461662292,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"AT ER UA TTL ALL>>173","id":173},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":2019}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":2019}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2019}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2019}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":2019}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":2019}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":486,"pathId":2019}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YAIVOKCSYDYBSV","smiles":"NC1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.49,"id":173,"pathId":2019}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[N+:8](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[NH2:8])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"AT ER UA TTL ALL>>332","id":332},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OKOSPWNNXVDXKZ","smiles":"ClC(=O)CC=C","intrinsicScore":0.49,"id":332,"pathId":2019}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"IWZIUQVIZQCEDY","smiles":"[O-][N+]1=CN=C(NC2=CC=C(F)C(Cl)=C2)C2=C1C=C(OCCCCl)C(NC(=O)C=C)=C2","intrinsicScore":0.24,"id":40,"pathId":2019}],"RXN":"C=CCC(=O)Cl.c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCCCl)N)Cl)F>>C=CC(=O)Nc1cc2c(cc1OCCCCl)[n+](cnc2Nc3ccc(c(c3)Cl)F)[O-];0.0;Unrecognized"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":2019}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCCl)[n+](cnc2Nc3ccc(c(c3)Cl)F)[O-]>C1COCC1.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCCl)ncnc2Nc3ccc(c(c3)Cl)F;0.0;Unrecognized"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":2019}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2019}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-7.847","depth":0,"reaction":{"label":">>0","id":0,"pathId":225},"children":[{"depth":1,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002493739128112793,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975062608718872,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.00285494327545166,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971450567245483,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.002886652946472168,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971133470535278,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003403782844543457,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9965962171554565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003649115562438965,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.996350884437561,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"LR ALL>>28","id":28},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006411254405975342,\"rxn_id\":\"ord-73de563950e54f3a8a473ab1f9c7e3c2\",\"index\":86652,\"rxn_smiles\":\"CN(C)C=O.O.O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12.OCC1CC1.[H-].[Na+]>>O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"procedure_details\":\"Cyclopropylmethyl alcohol (0.921 ml, 11.4 mmol) was added to a stirring suspension of NaH (455 mg, 11.4 mmol) in DMF (20 ml) under an argon atmosphere. The resulting solution was allowed to stir at RT for 20 min. 6-chloro-7-fluoro-8-nitro-9H-β-carboline (500 mg, 1.9 mmol) was added to the stirring solution and the resulting mixture was allowed to stir at RT. Upon addition of H2O, a brown solid precipitated out which was filtered to give the desired 6-chloro-7-cyclopropylmethyoxy-8-nitro-9H-β-carboline (510 mg, 85%). 1H-NMR (300 MHz, DMSO-d6): δ 0.35 (m, 2H), 0.59 (m, 2H), 1.32 (m, 1H), 4.04 (d, 2H), 8.21 (d, 1H), 8.46 (d, 1H), 8.90 (s, 1H), 9.02 (s, 1H), 12.32 (b, 1H). Retention Time (LC, method: ammonium acetate standard): 2.63 min. MS (M+H+): 318.\",\"reactant_000\":\"O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12\",\"reactant_002\":null,\"reactant_001\":\"OCC1CC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9935887455940247,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1F)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1[O:5][CH2:4][CH:1]1[CH2:3][CH2:2]1)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1\",\"yield_000\":84.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006817042827606201,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9931829571723938,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.007981956005096436,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9920180439949036,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00798940658569336,\"rxn_id\":\"ord-e13729e09b02453d8b2ae8502f41e869\",\"index\":593117,\"rxn_smiles\":\"CC(C)(C)[O-].CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-].OCC(F)F.[K+]>>CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"procedure_details\":\"The subtitle compound is prepared from N-(4-bromophenyl)-2-fluoro-4-methylamino-5-nitro-benzamide, 2,2-difluoroethanol and KOtBu in analogy to example 1e.\",\"reactant_000\":\"CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9920105934143066,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2F)=[CH:4][CH:3]=1.[F:23][CH:24]([F:27])[CH2:25][OH:26].CC([O-])(C)C.[K+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2[O:26][CH2:25][CH:24]([F:27])[F:23])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008773088455200195,\"rxn_id\":\"ord-c07b2acbc69f47289d653f004b6d071c\",\"index\":64408,\"rxn_smiles\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12.Cl.OCC(F)F.[H-].[Na+]>>COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"procedure_details\":\"Sodium hydride (1.21 g, 30 mmol, as a 60% suspension in mineral oil) was charged into a round bottom flask equipped with magnetic stirring and a nitrogen blanket, washed twice with 10 mL hexanes, dried of residual hexanes under a nitrogen stream, and suspended in 1,2-dimethoxyethane (20 mL). After cooling in an ice bath to about 10° C., 2-fluoro-6-trifluoromethyl-N-(5, 8-di-methoxy[ 1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide (4.21 g, about 98.5% purity, 10 mmol) was added over about 5 min, rinsing in with 1 mL 1,2-dimethoxyethane. A slight exotherm to about 13° C. occurred. Continued ice bath cooling lowered temperature to about 6° C. over about 10 min. To the off-white suspension was added 2,2-difluoroethanol (0.815 niL, 13 mmol) over about 5 min. A slight exotherm to about 13° C. occurred. The light tan suspension was stirred at about 5-10° C. for about 1 hr, then the ice bath was removed. The temperature peaked at about 28° C. (about 2° C. above room temperature) about 0.5 hr later. The tan suspension was stirred overnight (about 20 hr total reaction time), then worked up by addition of the reaction mixture over about 7 min into 5% hydrochloric acid (80 mL, 112 mmol) at about 5-10° C. with ice bath cooling. The suspension was stirred about 18 min at about 9° C., then filtered, washed twice with 15 mL water each, washed twice with 15 mL methanol each, air-dried for about 2 hr, and finally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide to afford the product as a white powder (4.34 g, about 92.8% purity, 8.3 mmol, about 83% yield).\",\"reactant_000\":\"OCC(F)F\",\"reactant_002\":null,\"reactant_001\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9912269115447998,\"agent_000\":\"Cl\",\"agent_001\":\"[H-]\",\"agent_002\":\"[Na+]\",\"temperature\":10.0,\"product_000\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"rxn_str\":\"[H-].[Na+].F[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15].[F:31][CH:32]([F:35])[CH2:33][OH:34].Cl>>[F:31][CH:32]([F:35])[CH2:33][O:34][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:11])([F:12])[F:13])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15]\",\"yield_000\":83.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>228","id":228},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.0052683353424072266,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9947316646575928,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005525708198547363,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944742918014526,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.005835771560668945,\"rxn_id\":\"ord-6569ee74ee084f45aee0cc6bab387a3a\",\"index\":556261,\"rxn_smiles\":\"BrBr.CC(=O)O.Nc1ccc2nc(C(F)(F)F)[nH]c2c1>>Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"procedure_details\":\"To a solution of 3.2 g (16 mmol) of 2-trifluoromethyl-5-aminobenzimidazole in 50 ml of AcOH was added 0.34 ml (6.6 mmol) of Br2 dropwise and resulting reaction mixture was stirred for 1 h at 25° C. The reaction mixture was concentrated in vacuo and purified on silica gel column chromatography (10% MeOH\\/CHCl3) to yield 1.7 g (6.2 mmol, 94%) of the desired product.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.994164228439331,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"rxn_str\":\"[F:1][C:2]([F:14])([F:13])[C:3]1[NH:4][C:5]2[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[Br:15]Br>CC(O)=O>[F:14][C:2]([F:1])([F:13])[C:3]1[NH:4][C:5]2[C:11]([Br:15])=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1\",\"yield_000\":93.9},{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.005841076374053955,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994158923625946,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005856215953826904,\"rxn_id\":\"ord-1d443c1852a24a44bc10d8df0c32bd94\",\"index\":784164,\"rxn_smiles\":\"BrBr.ClC(Cl)Cl.Nc1ccc2ncsc2c1>>Nc1ccc2ncsc2c1Br\",\"procedure_details\":\"To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67 mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27 mmol) in CHCl3 (10 ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5:1) to give 7-bromobenzo[d]thiazol-6-amine (80 mg, 80%).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncsc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941437840461731,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ncsc2c1Br\",\"rxn_str\":\"[S:1]1[C:5]2[CH:6]=[C:7]([NH2:10])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Br:11]Br>C(Cl)(Cl)Cl>[Br:11][C:6]1[C:5]2[S:1][CH:2]=[N:3][C:4]=2[CH:9]=[CH:8][C:7]=1[NH2:10]\",\"yield_000\":129.3}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>528","id":528},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":225}]},{"depth":7,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":225}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":225}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":225}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.3,"id":159,"pathId":225}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.3,"id":522,"pathId":225}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CUHXEXBIVQEVJM","smiles":"[O-][N+](=O)C1=CC2=C(N=CN=C2NC2=CC(Cl)=C(F)C=C2)C(Br)=C1F","intrinsicScore":0.33,"id":528,"pathId":225}],"RXN":"[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([cH:11][c:3]3[n:2][cH:1][n:23]2)[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22].[Br:24]Br>>[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([c:11]([c:3]3[n:2][cH:1][n:23]2)[Br:24])[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22];10.1.1;Bromination"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.33,"id":43,"pathId":225}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"JWFJQOCJPWGBQR","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C(Br)=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1","intrinsicScore":0.71,"id":228,"pathId":225}],"RXN":"[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])F)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>>[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":225}],"RXN":"[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:26])[F:30]>>[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:26])[F:30];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":225}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":225}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":225}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.856","depth":0,"reaction":{"label":">>0","id":0,"pathId":2055},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.002469778060913086,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9975302219390869,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.002480626106262207,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9975193738937378,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(C(C)C)C(C)C\",\"distance\":0.0029109716415405273,\"rxn_id\":\"ord-fbc6602e838844ea8049e8f1cc4695df\",\"index\":724691,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"procedure_details\":\"Diisopropylethylamine (0.09 ml, 0.5 mmol) was added in one portion to a stirred solution of 4-amino-N-(2-morpholin-4-yl-ethyl)-benzenesulfonamide (0.1 g, 0.35 mmol) in THF (3 ml) at room temperature. To this mixture was added acryloyl chloride (0.03 ml, 0.38 mmol) in one portion and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After this time, the mixture was concentrated under vacuum and the resulting residue purified by Prep HPLC to give the title compound (6 mg, 5% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9970890283584595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1\",\"rxn_str\":\"C(N(C(C)C)CC)(C)C.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[N:23]1([CH2:22][CH2:21][NH:20][S:17]([C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:16][CH:15]=2)(=[O:19])=[O:18])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1\",\"yield_000\":5.1},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0030384063720703125,\"rxn_id\":\"ord-3e531f95b682495d934d2f5fe24064c6\",\"index\":208714,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"procedure_details\":\"4-(4-Amino-benzenesulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.25 g, 0.67 mmol) was dissolved in THF (10 ml). To this was added diisopropylethylamine (0.33 ml, 1.9 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.06 ml, 0.74 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material was purified by column chromatography (elution: 20% heptane, 80% ethyl acetate) to give the title compound (57 mg, 20% yield) as a white powder.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9969615936279297,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)cc1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:36](=[O:39])[CH:37]=[CH2:38])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":19.8},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.003479301929473877,\"rxn_id\":\"ord-2a9510bf8eea48eb89d49af6327453f4\",\"index\":594742,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(C(C)C)C(C)C.Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1>>C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"procedure_details\":\"4-(4-Amino-2-trifluoromethyl-benzensulfonyl)-piperazine-1-carboxylic acid benzyl ester (0.44 g, 0.11 mmol) was dissolved in THF (15 ml). To this solution was added diisopropylethylamine (0.52 ml, 0.33 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.09 ml, 0.11 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material, was purified by preparative HPLC to give the title compound (70 mg, 14% yield) as a white solid.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9965206980705261,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)OCc3ccccc3)CC2)c(C(F)(F)F)c1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=2[C:27]([F:30])([F:29])[F:28])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42]>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:40](=[O:43])[CH:41]=[CH2:42])=[CH:22][C:21]=2[C:27]([F:30])([F:28])[F:29])(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":127.9}]","literatureScore":1,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":2055}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":2055}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":2055}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":2055}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2055}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2055}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":2055}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":2055}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":2055}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.62,"id":37,"pathId":2055}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.62,"id":7,"pathId":2055}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2055}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:22]1[cH:23][c:24]([c:25]([cH:27][c:21]1[NH:20][c:19]2[c:18]3[cH:33][c:34]([c:15]([cH:16][c:17]3[n+:31]([cH:30][n:29]2)[O-:32])[O:14][CH2:13][CH2:12][CH2:11][N:10]4[CH2:5][CH2:6][O:7][CH2:8][CH2:9]4)[NH2:35])[Cl:26])[F:28]>C1CCOC1.C(N(CC)C(C)C)(C)C>[CH2:4]=[CH:3][C:1](=[O:2])[NH:35][c:34]1[cH:33][c:18]2[c:17]([cH:16][c:15]1[O:14][CH2:13][CH2:12][CH2:11][N:10]3[CH2:5][CH2:6][O:7][CH2:8][CH2:9]3)[n+:31]([cH:30][n:29][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:25]([cH:27]4)[Cl:26])[F:28])[O-:32];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2055}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-7.86","depth":0,"reaction":{"label":">>0","id":0,"pathId":689},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0016717910766601562,\"rxn_id\":\"ord-7f4e5cc36887435cbbdc295e9f320425\",\"index\":760420,\"rxn_smiles\":\"C=CC(=O)O.Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1>>C=CC(=O)Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"procedure_details\":\"In a procedure analogous to Example 15, reaction of N1-(4-(pyridin-2-ylthio)pyrimidin-2-yl)benzene-1,3-diamine (35 mg, 0.12 mmol) and acrylic acid (16 μL, 0.24 mmol) furnished the product (18 mg, 43%).\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9983282089233398,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=2)[N:9]=1.[C:22](O)(=[O:25])[CH:23]=[CH2:24]>>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:16]=[C:17]([NH:21][C:22](=[O:25])[CH:23]=[CH2:24])[CH:18]=[CH:19][CH:20]=2)[N:9]=1\",\"yield_000\":42.9},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0018631219863891602,\"rxn_id\":\"ord-8b1771262c5e44ada19659657c7eb43e\",\"index\":412829,\"rxn_smiles\":\"C=CC(=O)O.Nc1cccc(Sc2ccnc(Cl)n2)c1>>C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"procedure_details\":\"In a procedure analogous to Example 15, reaction of 3-(2-chloropyrimidin-4-ylthio)benzenamine (300 mg, 1.26 mmol) and acrylic acid (173 μL, 2.52 mmol) furnished the product (250 mg, 68%).\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981368780136108,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"rxn_str\":\"[Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH2:15])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:16](O)(=[O:19])[CH:17]=[CH2:18]>>[Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1\",\"yield_000\":68.0},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004402875900268555,\"rxn_id\":\"ord-4094429492154f2dbcefff644399bdf5\",\"index\":480696,\"rxn_smiles\":\"C=CC(=O)O.CCN=C=NCCCN(C)C.CN(C)C=O.Cl.Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"procedure_details\":\"To a solution of 6-amino-4-[(3-bromophenyl)amino]-quinazoline (2.0 g, 6.35 mmol) in dry DMF (20 mL) under N2 was added acrylic acid (12.7 mmol, 0.87 mL). The resulting solution was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl) (7.62 mmol, 1.46 g) was added. The reaction was stirred at 0° C. for 15 minutes and then allowed to warm to room temperature and stirred for a further 2 hours, after which additional acrylic acid (0.30 mL) and EDCI·HCL (0.30 g) were added. After a further 2 hours, the reaction was complete by tlc, solvent was removed under reduced pressure, and the resulting residue diluted with saturated NaHCO3 and repeatedly extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Column chromatography on grade III alumina eluting with EtOAc\\/MeOH (95:5) followed by recrystallization from EtOAc\\/hexane gave a spongy white solid, which upon several hours under high vacuum gave N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.06 g, 45%) as a cream powder, mp 258-261° C.\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9955971240997314,\"agent_000\":\"CCN=C=NCCCN(C)C\",\"agent_001\":\"Cl\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1.[C:20](O)(=[O:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:20](=[O:23])[CH:21]=[CH2:22])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:18]=[CH:17][CH:16]=1\",\"yield_000\":45.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004851937294006348,\"rxn_id\":\"ord-f02e414320974bea8fe4ad495ef6df84\",\"index\":288038,\"rxn_smiles\":\"C\\/C=C\\/C(=O)O.Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1>>C\\/C=C\\/C(=O)Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1\",\"procedure_details\":\"(E)-N-(3-(4-(4-phenoxyphenoxy)pyridin-3-yl)phenyl)but-2-enamide was prepared from 3-(4-(4-phenoxyphenoxy)pyridin-3-yl)aniline and (E)-but-2-enoic acid using Method E (56% yield). HPLC: 98%, RT=4.292 min. MS: m\\/z=423 [M+H]+, RT=4.28 min. 1H-NMR (DMSO-d6) δ 9.91 (s, 1H), 8.52 (s, 1H), 8.43 (d, 1H), 7.92 (s, 1H), 7.68 (d, 1H), 7.40-7.37 (m, 3H), 7.30 (d, 1H), 7.18-7.12 (m, 3H), 7.08 (d, 2H), 7.02 (d, 2H), 6.83-6.76 (m, 2H), 6.14 (d, 1H), 1.86 (d, 3H).\",\"reactant_000\":\"C\\/C=C\\/C(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951480627059937,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C\\/C=C\\/C(=O)Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1\",\"rxn_str\":\"[O:1]([C:8]1[CH:27]=[CH:26][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=2)[NH2:22])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28](O)(=[O:32])\\/[CH:29]=[CH:30]\\/[CH3:31]>>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:20]=[C:21]([NH:22][C:28](=[O:32])\\/[CH:29]=[CH:30]\\/[CH3:31])[CH:23]=[CH:24][CH:25]=2)=[CH:26][CH:27]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":56.0},{\"solvent_000\":\"CO\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.004852771759033203,\"rxn_id\":\"ord-bf24e611fd8c4b079f2ff4859f73f6ab\",\"index\":267419,\"rxn_smiles\":\"C=CC(=O)O.CCN=C=NCCCN(C)C.CN(C)C=O.CO.Cl.Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1>>C=CC(=O)Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"procedure_details\":\"To an ice-cold solution of 0.158 g (0.5 mM) of 7-amino-4-(3-bromoanilino)-quinazoline [J Med Chem, 1995:3482] and 0.108 g of acrylic acid in 5.0 mL of dry dimethylformamide (DMF) was added 0.288 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (EDAC). After stirring for 5 minutes, the mixture became a solution, and the ice bath was removed. The reaction continued to stir at room temperature for 3 hours. The reaction was then poured into a mixture of ice and water and made basic with the addition of a saturated solution of sodium bicarbonate. This aqueous mixture was extracted three times with ethyl acetate, and the pooled extracts were dried over magnesium sulfate. The solution was filtered and concentrated in vacuo to afford a light yellow solid. The solid was dissolved in 100 mL of methanol, filtered, and concentrated in vacuo to approximately 10 mL. The solid which precipitated from solution was collected and dried in vacuo at 80° C. to give 50 mg of N-[4-(3-bromo-phenylamino)-quinazolin-7-yl]acrylamide, mp >265° C. Chemical ionization mass spectra: m\\/e 369.\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9951472282409668,\"agent_000\":\"CCN=C=NCCCN(C)C\",\"agent_001\":\"Cl\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:20](O)(=[O:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CO>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:6]2[C:5]3[C:10](=[CH:11][C:2]([NH:1][C:20](=[O:23])[CH:21]=[CH2:22])=[CH:3][CH:4]=3)[N:9]=[CH:8][N:7]=2)[CH:18]=[CH:17][CH:16]=1\",\"yield_000\":27.0}]","literatureScore":1,"label":"T5 AT UA TTL ER ALL>>12","id":12},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002769649028778076,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9972303509712219,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0031270384788513184,\"rxn_id\":\"ord-dcc1a5efa86d4d09b08ec14f86ec1748\",\"index\":264188,\"rxn_smiles\":\"Cl.O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12>>Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"procedure_details\":\"A solution of stannous chloride dihydrate (3.7 g, 16 mmol) in 10 ml of conc. hydrochloric acid was added dropwise to a stirred suspension of 2,3-dihydroxy-6-nitrobenzo(f)quinoxaline (1.3 g, 5 mmol) in 8 ml of conc. hydrochloric acid. Then the mixture was stirred at 60-70° C. on an oil bath for 2 h. After cooling on ice, the precipitate was collected, dissolved in boiling water (1 1), filtered while hot, and neutralized to pH 6 with solid sodium hydrogen carbonate. The yellow product was isolated and recrystallized from DMF\\/water, washed with water, ethanol and ether and finally dried at 110 ° C. to give 0.90 g (63%) of pure title compound, m.p. >300° C., IR (KBr): 1690, ? 1640 and 1605 cm-1,1H-NMR (DMSO-d6): 5.8 (broad s, 2H,NH2), 6.63(s,1H, H-5), 7.2-8.7 (m, 4H, ArH), 11.8 (broad s, 2H, 20H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968729615211487,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([OH:19])=[N:4][C:5]2[CH:6]=[C:7]([N+:16]([O-])=O)[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[N:11]=1>Cl>[NH2:16][C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]2[N:11]=[C:2]([OH:1])[C:3]([OH:19])=[N:4][C:5]=2[CH:6]=1\",\"yield_000\":79.2},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.00328141450881958,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9967185854911804,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003656148910522461,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963438510894775,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003899812698364258,\"rxn_id\":\"ord-fc93af0f0d9a40e284c2500298acaf93\",\"index\":573049,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"The crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine was dissolved in THF and reduced using Raney nickel catalyst to yield N4-(3-Chloro-4-fluoro-phenyl)-7-(2,2-difluoro-ethoxy)-quinazoline-4,6-diamine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961001873016357,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C1COCC1.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null}]","literatureScore":1,"label":"UA CF T5 AT ER TTL ALL>>33","id":33},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":689}]},{"depth":5,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":689}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":689}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":4,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":689}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.68,"id":154,"pathId":689}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEFNIUDZICAGOU","smiles":"NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1O","intrinsicScore":0.65,"id":33,"pathId":689}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[N+:21](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[NH2:21])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.65,"id":6,"pathId":689}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ZZFBJRRZEBIWHH","smiles":"OC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1NC(=O)C=C","intrinsicScore":0.024,"id":12,"pathId":689}],"RXN":"[CH2:4]=[CH:3][C:2](=[O:1])O.[cH:11]1[cH:12][c:5]([c:7]([cH:9][c:10]1[NH:13][c:14]2[c:15]3[cH:20][c:19]([c:18]([cH:17][c:16]3[n:23][cH:24][n:25]2)[OH:22])[NH2:21])[Cl:8])[F:6]>>[CH2:4]=[CH:3][C:2](=[O:1])[NH:21][c:19]1[cH:20][c:15]2[c:16]([cH:17][c:18]1[OH:22])[n:23][cH:24][n:25][c:14]2[NH:13][c:10]3[cH:11][cH:12][c:5]([c:7]([cH:9]3)[Cl:8])[F:6];2.1.2;Carboxylic"},{"depth":1,"reaction":{"label":"AT T5 ER UA TTL ALL>>13","id":13},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"PIAZYBLGBSMNLX","smiles":"ClCCCN1CCOCC1","intrinsicScore":0.024,"id":13,"pathId":689}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":689}],"RXN":"[CH2:1]=[CH:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][c:8]2[c:22]([cH:23][c:24]1[OH:25])[n:21][cH:20][n:19][c:9]2[NH:10][c:11]3[cH:12][cH:13][c:14]([c:16]([cH:18]3)[Cl:17])[F:15].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][N:29]1[CH2:28][CH2:27][CH2:26]Cl>>[CH2:1]=[CH:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][c:8]2[c:22]([cH:23][c:24]1[O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:21][cH:20][n:19][c:9]2[NH:10][c:11]4[cH:12][cH:13][c:14]([c:16]([cH:18]4)[Cl:17])[F:15];1.7.9;Williamson"},{"pathScore":"-7.868","depth":0,"reaction":{"label":">>0","id":0,"pathId":1534},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1534}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1534}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":1534}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":1534}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":1534}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":5,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":1534}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":1534}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1534}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1534}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1534}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1534}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1534}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-7.879","depth":0,"reaction":{"label":">>0","id":0,"pathId":1499},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":1499}]},{"depth":7,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":1499}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":1499}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1499}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":1499}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":1499}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":1499}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1499}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1499}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1499}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1499}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1499}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-7.883","depth":0,"reaction":{"label":">>0","id":0,"pathId":8},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0029944181442260742,\"rxn_id\":\"ord-e0b0f01cfc8846efa4465e6a5288872d\",\"index\":23488,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (1.5 g, 2.96 mmol), 4-(3-hydroxypropyl)morpholine (0.623 mL, 4.5 mmol), triphenylphosphine (1.18 g, 4.5 mmol), and dichloromethane (50 mL) was added diisopropyl azodicarboxylate (0.886 mL, 4.5 mmol). The mixture was stirred at room temperature for 16 h, monitored by LCMS. After removal of solvent, the crude mixture was separated by flash column chromatography (silica), eluting with 5% methanol in dichloromethane to give N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N\\u2032-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (890 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.36 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.83 (m, 1H), 7.64 (m, 2H), 7.57 (s, 1H), 7.44 (m, 3H), 7.18 (t, 2H), 4.27 (m, 2H), 3.99 (s, 3H), 3.61 (m, 6H), 2.40 (m, 4H), 2.01 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.3.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9970055818557739,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:37][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:36][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1\",\"yield_000\":47.5},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CCOCC\",\"distance\":0.003035128116607666,\"rxn_id\":\"ord-fab5133cf99a4d628c51ef65011713b7\",\"index\":182883,\"rxn_smiles\":\"CCCCP(CCCC)CCCC.CCOCC.COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O.ClCCl.O=C(N=NC(=O)N1CCCCC1)N1CCCCC1.OCCN1CCSCC1>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"procedure_details\":\"4-(2-Hydroxyethyl)thiomorpholine (114 mg, 0.78 mmol), (J. Am. Chem. Soc. 1934. 56, 1720), in methylene chloride (1 ml) followed by 1,1\\u2032-(azodicarbonyl)dipiperidine (525 mg. 2.08 mmol) were added to a stirred solution of 4-(4-chloro-2-fluoroanilino)7-hydroxy-6 methoxyquinazoline (225 mg, 0.70 mmol), (prepared as described for the starting material in Example 2), and tributylphosphine (0.51 ml, 2.08 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours and allowed to stand for a further 18 hours. Ether (8 ml) was added, the precipitate removed by filtration and the solvent removed from the filtrate by evaporation. The residue was dissolved in acetone and ethereal hydrogen chloride (2.5 m! of a 1M solution) added. The precipitated product was collected by filtration and purified by column chromatography eluting with methylene chloride\\/methanol\\/aqueous ammonia (150\\/8\\/1). The purified product was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazoline (70 mg, 22%) as a pale yellow solid.\",\"reactant_000\":\"OCCN1CCSCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O\",\"rxn_time\":3.5,\"reactant_003\":null,\"similarity\":0.9969648718833923,\"agent_000\":\"CCCCP(CCCC)CCCC\",\"agent_001\":\"O=C(N=NC(=O)N1CCCCC1)N1CCCCC1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][S:7][CH2:6][CH2:5]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40](O)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([O:1][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][S:7][CH2:6][CH2:5]4)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1\",\"yield_000\":22.3},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0032836198806762695,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9967163801193237,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0037235617637634277,\"rxn_id\":\"ord-ae2e2a15cfb44e3c8c0bddafaf4489b5\",\"index\":501292,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O.OCCc1ccncc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"procedure_details\":\"To a solution of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea (0.1 g, 0.24 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and triphenylphosphine (0.0944 g, 0.36 mmol) in 10 mL of dry THF was added diisopropylazo-dicarboxylate (0.0728 g, 0.36 mmol) at ambient temperature. The mixture was stirred for 2 hours. Next, additional triphenylphosphine (0.0944 g, 0.36 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and diisopropylazodicarboxylate were added and the reaction mixture further stirred at room temperature overnight. The solvent from the reaction mixture was evaporated and the crude residue was dissolved in 5.0 mL of DMSO and purified by RP-HPLC. The proper fractions were collected and concentrated to ¼ volume. The aqueous solution was neutralized with 1N NaOH and extracted with ethyl acetate (2×, 59 mL). The organic layer was dried with sodium sulfate, filtered and evaporated to dryness to afford 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyridin-4-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea as a brown solid in 44% yield. LCMS m\\/z (%)=526 (M+H 79Br, 100), 528 (M+H 81Br, 67). 1H NMR (DMSO-d6) δ: 9.33 (bs, 1H), 9.24 (bs, 1H), 8.39 (dd, J=4.44 and 1.48 Hz, 2H), 7.63 (d, J=7.28 Hz, 1H), 7.59 (s, 1H), 7.56 (dd, J=8.94 and 2.71 Hz, 2H), 7.48 (m, 1H), 7.34 (d, J=2.67, 1H), 7.31 (d, J=2.67, 1H), 7.28 (dd, J=6.88 and 4.87 Hz, 2H), 7.14 (d, J=9.05 Hz, 1H), 7.09 (d, J=5.93 Hz, 1H), 4.01-4.2 (m, 2H), 3.48 (s, 3H), 2.96-2.91 (m, 2H).\",\"reactant_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCc1ccncc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9962764382362366,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"rxn_str\":\"[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[OH:14].O[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[O:14][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1\",\"yield_000\":44.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0038225650787353516,\"rxn_id\":\"ord-33bfcf35bf734b52b59d70aa5d195f4f\",\"index\":462262,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Diethyl azodicarboxylate (2.67 ml, 17 mmol) was added dropwise to a solution of 3-morpholinopropan-1-ol (1.54 g, 10 mmol), 7-hydroxy-3,4-dihydro-6-methoxy-3-((pivaloyloxy)methyl)quinazolin-4-one (2.6 g, 8.5 mmol) and triphenylphosphine (4.45 g, 17 mmol) in methylene chloride (40 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride\\/methanol (97\\/3 followed by 95\\/5) to give 3,4-dihydro-6-methoxy-3-((pivaloyloxy)metyl)-7-(3-morpholinopropoxy)quinazolin-4-one (3.6 g, 97%).\",\"reactant_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961774349212646,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]1.O[C:24]1[CH:33]=[C:32]2[C:27]([C:28](=[O:42])[N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[N:31]2)=[CH:26][C:25]=1[O:43][CH3:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:44][O:43][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:24]=1[O:22][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[N:31]=[CH:30][N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]2=[O:42]\",\"yield_000\":97.7}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":8}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":8}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":8}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":8}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":8}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":8}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.42,"id":154,"pathId":8}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":3,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":8}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":8}],"RXN":"[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[OH:17])[N+:19](=[O:21])[O-:20])[Cl:3])[F:5].[CH2:25]1[CH2:26][O:27][CH2:28][CH2:29][N:24]1[CH2:30][CH2:31][CH2:32]O>C(C)CCP(CCCC)CCCC.ClCCl.C1CN(CCC1)C(N=NC(N2CCCCC2)=O)=O>[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:32][CH2:31][CH2:30][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[N+:19](=[O:21])[O-:20])[Cl:3])[F:5];1.7.7;Mitsunobu"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":8}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":8}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":8}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.893","depth":0,"reaction":{"label":">>0","id":0,"pathId":291},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":291}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":291}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":291}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":291}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":291}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":291}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":291}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":291}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":291}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":291}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":291}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":291}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.905","depth":0,"reaction":{"label":">>0","id":0,"pathId":1517},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1517}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1517}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1517}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1517}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":1517}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":5,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":1517}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":1517}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1517}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1517}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1517}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1517}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1517}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-7.929","depth":0,"reaction":{"label":">>0","id":0,"pathId":311},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.2,"literature":"[{\"solvent_000\":\"CCO\",\"solvent_001\":\"O\",\"distance\":0.03514432907104492,\"rxn_id\":\"ord-ac830d54b7724a8b93da7678034827fa\",\"index\":571122,\"rxn_smiles\":\"CCO.Cc1cc(Br)c2nc(O)c[n+]([O-])c2c1.O.O=S([O-])S(=O)[O-].[Na+].[Na+]>>Cc1cc(Br)c2nc(O)cnc2c1\",\"procedure_details\":\"The title compound of Step C (25 g, 98 mmol) and sodium dithionite (38 g, 220 mmol) were suspended in a mixture of ethanol (1000 mL) and water (200 mL) at room temperature. After 1 h, most of the solvent was removed under reduced pressure. The residue was diluted with water and acidified with hydrochloric acid. Insolubles were removed by filtration. The filtrate was extracted twice with methylene chloride. The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure to afford the title compound of Step D as a tan\\/yellow solid (15.29 g, 65%). 1H NMR (CDCl3): δ2.37 (s,3H), 7.5 (d,2H), 8.15 (s, 1H), 9.8 (br s, 1H).\",\"reactant_000\":\"Cc1cc(Br)c2nc(O)c[n+]([O-])c2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9648556709289551,\"agent_000\":\"O=S([O-])S(=O)[O-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Br)c2nc(O)cnc2c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([OH:12])[CH:8]=[N+:7]2[O-].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([OH:12])[CH:8]=[N:7]2\",\"yield_000\":65.3},{\"solvent_000\":\"ClP(Cl)Cl\",\"solvent_001\":\"ClC(Cl)Cl\",\"distance\":0.03644132614135742,\"rxn_id\":\"ord-4ee3d8d301824f80b57afcbb6894ed3d\",\"index\":186003,\"rxn_smiles\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC.ClC(Cl)Cl.ClP(Cl)Cl>>COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"procedure_details\":\"A solution of N-oxide 3 (10 mM) and phosphorus trichloride (30 mM) in anhydrous chloroform (100 ml) was refluxed for 7 h. Solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulphate and then evaporated under reduced pressure. The residue was recrystallized from isopropanol to provide the title dimethyl quinoline-2,3-dicarboxylate 7 as an off white (or light yellow) powder.\",\"reactant_000\":\"COC(=O)c1cc2ccccc2[n+]([O-])c1C(=O)OC\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9635586738586426,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)c1cc2ccccc2nc1C(=O)OC\",\"rxn_str\":\"[N+:1]1([O-])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16].P(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[C:2]=1[C:15]([O:17][CH3:18])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1=CCCCC1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.04215782880783081,\"rxn_id\":\"ord-e79e74c481414470aec1b7e2b799dffb\",\"index\":735026,\"rxn_smiles\":\"C1=CCCCC1.CC(C)O.COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1.[Pd]>>COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"procedure_details\":\"A mixture of 7-({2-[(4-methoxybenzyl)amino]-1-oxidopyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (21.1 g, 0.0502 mol), cyclohexene (100 mL, 0.9 mol) and Pd (10% on Carbon, 4.5 g) in isopropyl alcohol (400 mL, 5 mol) was heated at 85° C. overnight. Additional catalyst (2.5 g) and cyclohexene (30 mL) were added. The mixture was heated at 90° C. overnight and then filtered. The filtrate was concentrated to give 7-({2-[(4-methoxybenzyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid which was used in the next step without purification. LCMS ES+ 405.7\",\"reactant_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9578421711921692,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":85.0,\"product_000\":\"COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N+:10]=2[O-])=[CH:5][CH:4]=1.C(O)(C)C>[Pd].C1CCCCC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[CH:30][CH:31]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.04627472162246704,\"rxn_id\":\"ord-41f86ab7b419465b93bad7cb1b735ee9\",\"index\":112985,\"rxn_smiles\":\"CC(=O)O.COc1cc[n+]([O-])c(NCCN(C(C)C)C(C)C)c1.[Fe]>>COc1ccnc(NCCN(C(C)C)C(C)C)c1\",\"procedure_details\":\"2-(2-diisopropylaminoethylamino)-4-methoxypyridine-N-oxide (4.3 g., 15 mmole) dissolved in glacial acetic acid (32 ml.) is refluxed with iron powder (8.2 g.) for three hours. The reaction mixture is filtered to remove insoluble salts and then the solvent evaporated. The residue is dissolved in methanol, treated with excess potassium hydroxide pellets and filtered to remove more insoluble salts. The concentrate solution is dissolved in chloroform, washed with water, dried over sodium sulfate, filtered through a pad of charcoal and evaporated to give oily product.\",\"reactant_000\":\"COc1cc[n+]([O-])c(NCCN(C(C)C)C(C)C)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.953725278377533,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccnc(NCCN(C(C)C)C(C)C)c1\",\"rxn_str\":\"[CH:1]([N:4]([CH:17]([CH3:19])[CH3:18])[CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][N+:9]=1[O-])([CH3:3])[CH3:2]>C(O)(=O)C.[Fe]>[CH:17]([N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][N:9]=1)([CH3:18])[CH3:19]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.05018347501754761,\"rxn_id\":\"ord-983f4b85a4c94a6e873248f98cfebcb3\",\"index\":368215,\"rxn_smiles\":\"CCCc1cc(OC)cc[n+]1[O-].O=S(=O)(O)O.[Zn]>>CCCc1cc(OC)ccn1\",\"procedure_details\":\"A solution of 4-methoxy-2-n-propylpyridine-N-oxide (59.3 g, 0.355 mol) in 800 ml of 1 M sulfuric acid was stirred and heated to 70-80° C. Zinc dust (140.0 g, 214 mol) was added in portions over four hours. When the addition was complete, heating was continued for a further eight hours. The resulting precipitate was filtered off and washed with water. The filtrate was made strongly alkaline by addition of a 32% sodium hydroxide solution and extracted with dichloromethane (3×250 ml). The extracts were combined, dried with sodium sulfate, filtered and evaporated to a yellow oil. Distillation (0.1-0.2 mbar, 44-46° C.) afforded 46.1 g (86%) of 4-methoxy-2-n-propylpyridine as a colourless oil. 1H-NMR (CDCl3, 200 MHz) δ: 0.99 (t, 3H), 1.75 (sext, 2H), 2.72 (t, 2H), 3.81 (s, 3H), 6.10-6.18 (m, 2H), 8.35 (d, 1H).\",\"reactant_000\":\"CCCc1cc(OC)cc[n+]1[O-]\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9498165249824524,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[Zn]\",\"agent_002\":null,\"temperature\":75.0,\"product_000\":\"CCCc1cc(OC)ccn1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N+:6]([O-])=[C:5]([CH2:10][CH2:11][CH3:12])[CH:4]=1>S(=O)(=O)(O)O.[Zn]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:10][CH2:11][CH3:12])[CH:4]=1\",\"yield_000\":85.9}]","literatureScore":0.96,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.014116823673248291,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9858831763267517,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.016109049320220947,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.983890950679779,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01629471778869629,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9837052822113037,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.017170846462249756,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9828291535377502,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.018261253833770752,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9817387461662292,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"AT ER UA TTL ALL>>173","id":173},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":311}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":311}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":311}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":311}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":311}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":311}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":486,"pathId":311}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YAIVOKCSYDYBSV","smiles":"NC1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.24,"id":173,"pathId":311}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[N+:8](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[NH2:8])[Cl:18])[F:20];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":311}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCCCl)N)Cl)F>C(C)O.Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCCl)N)Cl)F;0.0;Unrecognized"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":311}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":311}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":311}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":311}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.954","depth":0,"reaction":{"label":">>0","id":0,"pathId":228},"children":[{"depth":1,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002493739128112793,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975062608718872,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.00285494327545166,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971450567245483,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.002886652946472168,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971133470535278,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003403782844543457,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9965962171554565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003649115562438965,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.996350884437561,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"LR ALL>>28","id":28},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006411254405975342,\"rxn_id\":\"ord-73de563950e54f3a8a473ab1f9c7e3c2\",\"index\":86652,\"rxn_smiles\":\"CN(C)C=O.O.O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12.OCC1CC1.[H-].[Na+]>>O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"procedure_details\":\"Cyclopropylmethyl alcohol (0.921 ml, 11.4 mmol) was added to a stirring suspension of NaH (455 mg, 11.4 mmol) in DMF (20 ml) under an argon atmosphere. The resulting solution was allowed to stir at RT for 20 min. 6-chloro-7-fluoro-8-nitro-9H-β-carboline (500 mg, 1.9 mmol) was added to the stirring solution and the resulting mixture was allowed to stir at RT. Upon addition of H2O, a brown solid precipitated out which was filtered to give the desired 6-chloro-7-cyclopropylmethyoxy-8-nitro-9H-β-carboline (510 mg, 85%). 1H-NMR (300 MHz, DMSO-d6): δ 0.35 (m, 2H), 0.59 (m, 2H), 1.32 (m, 1H), 4.04 (d, 2H), 8.21 (d, 1H), 8.46 (d, 1H), 8.90 (s, 1H), 9.02 (s, 1H), 12.32 (b, 1H). Retention Time (LC, method: ammonium acetate standard): 2.63 min. MS (M+H+): 318.\",\"reactant_000\":\"O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12\",\"reactant_002\":null,\"reactant_001\":\"OCC1CC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9935887455940247,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1F)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1[O:5][CH2:4][CH:1]1[CH2:3][CH2:2]1)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1\",\"yield_000\":84.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006817042827606201,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9931829571723938,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.007981956005096436,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9920180439949036,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00798940658569336,\"rxn_id\":\"ord-e13729e09b02453d8b2ae8502f41e869\",\"index\":593117,\"rxn_smiles\":\"CC(C)(C)[O-].CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-].OCC(F)F.[K+]>>CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"procedure_details\":\"The subtitle compound is prepared from N-(4-bromophenyl)-2-fluoro-4-methylamino-5-nitro-benzamide, 2,2-difluoroethanol and KOtBu in analogy to example 1e.\",\"reactant_000\":\"CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9920105934143066,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2F)=[CH:4][CH:3]=1.[F:23][CH:24]([F:27])[CH2:25][OH:26].CC([O-])(C)C.[K+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2[O:26][CH2:25][CH:24]([F:27])[F:23])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008773088455200195,\"rxn_id\":\"ord-c07b2acbc69f47289d653f004b6d071c\",\"index\":64408,\"rxn_smiles\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12.Cl.OCC(F)F.[H-].[Na+]>>COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"procedure_details\":\"Sodium hydride (1.21 g, 30 mmol, as a 60% suspension in mineral oil) was charged into a round bottom flask equipped with magnetic stirring and a nitrogen blanket, washed twice with 10 mL hexanes, dried of residual hexanes under a nitrogen stream, and suspended in 1,2-dimethoxyethane (20 mL). After cooling in an ice bath to about 10° C., 2-fluoro-6-trifluoromethyl-N-(5, 8-di-methoxy[ 1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide (4.21 g, about 98.5% purity, 10 mmol) was added over about 5 min, rinsing in with 1 mL 1,2-dimethoxyethane. A slight exotherm to about 13° C. occurred. Continued ice bath cooling lowered temperature to about 6° C. over about 10 min. To the off-white suspension was added 2,2-difluoroethanol (0.815 niL, 13 mmol) over about 5 min. A slight exotherm to about 13° C. occurred. The light tan suspension was stirred at about 5-10° C. for about 1 hr, then the ice bath was removed. The temperature peaked at about 28° C. (about 2° C. above room temperature) about 0.5 hr later. The tan suspension was stirred overnight (about 20 hr total reaction time), then worked up by addition of the reaction mixture over about 7 min into 5% hydrochloric acid (80 mL, 112 mmol) at about 5-10° C. with ice bath cooling. The suspension was stirred about 18 min at about 9° C., then filtered, washed twice with 15 mL water each, washed twice with 15 mL methanol each, air-dried for about 2 hr, and finally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide to afford the product as a white powder (4.34 g, about 92.8% purity, 8.3 mmol, about 83% yield).\",\"reactant_000\":\"OCC(F)F\",\"reactant_002\":null,\"reactant_001\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9912269115447998,\"agent_000\":\"Cl\",\"agent_001\":\"[H-]\",\"agent_002\":\"[Na+]\",\"temperature\":10.0,\"product_000\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"rxn_str\":\"[H-].[Na+].F[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15].[F:31][CH:32]([F:35])[CH2:33][OH:34].Cl>>[F:31][CH:32]([F:35])[CH2:33][O:34][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:11])([F:12])[F:13])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15]\",\"yield_000\":83.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>228","id":228},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.0052683353424072266,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9947316646575928,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005525708198547363,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944742918014526,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.005835771560668945,\"rxn_id\":\"ord-6569ee74ee084f45aee0cc6bab387a3a\",\"index\":556261,\"rxn_smiles\":\"BrBr.CC(=O)O.Nc1ccc2nc(C(F)(F)F)[nH]c2c1>>Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"procedure_details\":\"To a solution of 3.2 g (16 mmol) of 2-trifluoromethyl-5-aminobenzimidazole in 50 ml of AcOH was added 0.34 ml (6.6 mmol) of Br2 dropwise and resulting reaction mixture was stirred for 1 h at 25° C. The reaction mixture was concentrated in vacuo and purified on silica gel column chromatography (10% MeOH\\/CHCl3) to yield 1.7 g (6.2 mmol, 94%) of the desired product.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.994164228439331,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"rxn_str\":\"[F:1][C:2]([F:14])([F:13])[C:3]1[NH:4][C:5]2[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[Br:15]Br>CC(O)=O>[F:14][C:2]([F:1])([F:13])[C:3]1[NH:4][C:5]2[C:11]([Br:15])=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1\",\"yield_000\":93.9},{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.005841076374053955,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994158923625946,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005856215953826904,\"rxn_id\":\"ord-1d443c1852a24a44bc10d8df0c32bd94\",\"index\":784164,\"rxn_smiles\":\"BrBr.ClC(Cl)Cl.Nc1ccc2ncsc2c1>>Nc1ccc2ncsc2c1Br\",\"procedure_details\":\"To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67 mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27 mmol) in CHCl3 (10 ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5:1) to give 7-bromobenzo[d]thiazol-6-amine (80 mg, 80%).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncsc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941437840461731,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ncsc2c1Br\",\"rxn_str\":\"[S:1]1[C:5]2[CH:6]=[C:7]([NH2:10])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Br:11]Br>C(Cl)(Cl)Cl>[Br:11][C:6]1[C:5]2[S:1][CH:2]=[N:3][C:4]=2[CH:9]=[CH:8][C:7]=1[NH2:10]\",\"yield_000\":129.3}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>528","id":528},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":228}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":228}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":228}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":228}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.3,"id":159,"pathId":228}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.3,"id":522,"pathId":228}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CUHXEXBIVQEVJM","smiles":"[O-][N+](=O)C1=CC2=C(N=CN=C2NC2=CC(Cl)=C(F)C=C2)C(Br)=C1F","intrinsicScore":0.33,"id":528,"pathId":228}],"RXN":"[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([cH:11][c:3]3[n:2][cH:1][n:23]2)[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22].[Br:24]Br>>[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([c:11]([c:3]3[n:2][cH:1][n:23]2)[Br:24])[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22];10.1.1;Bromination"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.33,"id":43,"pathId":228}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"JWFJQOCJPWGBQR","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C(Br)=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1","intrinsicScore":0.71,"id":228,"pathId":228}],"RXN":"[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])F)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>>[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":228}],"RXN":"[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:26])[F:30]>>[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:26])[F:30];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":228}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":228}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":228}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-7.986","depth":0,"reaction":{"label":">>0","id":0,"pathId":1502},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":1502}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":1502}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":1502}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":1502}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":1502}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":1502}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":1502}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1502}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1502}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1502}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1502}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1502}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.007","depth":0,"reaction":{"label":">>0","id":0,"pathId":1848},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":1848}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":1848}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":1848}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":1848}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1848}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1848}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1848}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1848}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1848}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1848}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1848}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1848}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-8.031","depth":0,"reaction":{"label":">>0","id":0,"pathId":121},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.6,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.008023500442504883,\"rxn_id\":\"ord-42dc5bd007e148f297483fd574a84112\",\"index\":514864,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCN(CC)CC.Cl.Cl.N#Cc1ccc(Cn2cncc2CCN)cc1F>>N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride (0.92 g, 0.0029 mmol) in acetonitrile (150 mL) and triethylamine (3.2 mL) was added 2-bromoethyl ether (0.839 mL, 0.0067 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in uacuo and the residue was dissolved in EtOAc which was washed twice with 1M HCl (100 mL). The HCl layers were combined and adjusted to pH=9 with solid Na2CO3 and extraxcted 3 times with EtOAc. The EtOAc layers were combined and dried with brine and MgSO4. Removal of the EtOAc in vacuo yielded the title compound which was used as is in the next step.\",\"reactant_000\":\"N#Cc1ccc(Cn2cncc2CCN)cc1F\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919764995574951,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=2)[CH:9]=[N:8][CH:7]=1.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>C(#N)C.C(N(CC)CC)C>[F:20][C:14]1[CH:13]=[C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][N:3]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:7][N:8]=[CH:9]2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.008291244506835938,\"rxn_id\":\"ord-08bb54aa0ab244ff90317c31f9d4c5e8\",\"index\":731783,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.NC1CCN(Cc2ccccc2)CC1.O=C([O-])[O-].[K+].[K+]>>c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"procedure_details\":\"To a stirred mixture of 4-amino-1-benzylpiperidine (1.53 mL, 7.5 mmol), K2CO3 (2.28 g, 16.5 mmol) and DMF (15 mL) heated at 50° C. was added dropwise over 60 min bis(2-bromoethyl) ether (0.96 mL, 7.65 mmol). After stirring for 6 hours at 80° C., the solvent was removed by blowing with a stream of nitrogen over 2 hours. The residue was purified on a silica gel column to give 1.7 g (87%) of 4-(1-benzyl-piperidin-4-yl)morpholine as a waxy solid.\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"NC1CCN(Cc2ccccc2)CC1\",\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9917087554931641,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"rxn_str\":\"[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>CN(C=O)C>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:1]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1\",\"yield_000\":87.1},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.008305191993713379,\"rxn_id\":\"ord-ac7a693c46694fd5b13039f5c104d79e\",\"index\":134482,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N.O=C([O-])[O-].[K+].[K+]>>CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"procedure_details\":\"cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane\\/methanol\\/ammonia 100:0:0->140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m\\/e=403.3 [(M+H)+].\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9916948080062866,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"rxn_str\":\"[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]\",\"yield_000\":68.6},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.00859677791595459,\"rxn_id\":\"ord-aa3eb88c8e6c445794e16d41429514f0\",\"index\":719114,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O.CCN(CC)CC.Cl.Cl>>CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-2-methyl-imidazol-1-ylmethyl]-2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile dihydrochloride (as described in Example 11) (0.25 g, 0.456 mmol) in acetonitrile (35.0 mL) and triethylamine (1.8 mL) was added 2-bromoethyl ether (0.133 mL, 1.06 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in vacuo to obtain the title compound after purification by preparative HPLC.\",\"reactant_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9914032220840454,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]4([CH2:36][CH3:37])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]4=[O:35])[CH:22]=3)[CH:13]=2)[C:9]([CH3:38])=[N:8][CH:7]=1.Br[CH2:40][CH2:41][O:42][CH2:43][CH2:44]Br>C(#N)C.C(N(CC)CC)C>[CH2:36]([C:27]1([C:23]2[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=2)[O:20][C:14]2[CH:13]=[C:12]([CH2:11][N:10]3[C:6]([CH2:5][CH2:4][N:3]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[CH:7][N:8]=[C:9]3[CH3:38])[CH:19]=[CH:18][C:15]=2[C:16]#[N:17])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]1=[O:35])[CH3:37]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.008690357208251953,\"rxn_id\":\"ord-90e436a959164d40ab8c094946564425\",\"index\":740936,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.Nc1ccc(Br)c(Cl)c1.O.O=C([O-])[O-].[I-].[K+].[K+].[K+]>>Clc1cc(N2CCOCC2)ccc1Br\",\"procedure_details\":\"4-Bromo-3-chloroaniline (500 mg) was dissolved in DMF (10 ml), and bis(2-bromoethyl)ether (1.12 g), K2CO3 (1.34 g), and potassium iodide (80 mg) were added thereto, followed by stirring at 80° C. for 2 days. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 20% EtOAc\\/hexane) to obtain 4-(4-bromo-3-chlorophenyl)morpholine (263 mg).\",\"reactant_000\":\"Nc1ccc(Br)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":48.0,\"reactant_003\":null,\"similarity\":0.991309642791748,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[I-]\",\"agent_002\":\"[K+]\",\"temperature\":80.0,\"product_000\":\"Clc1cc(N2CCOCC2)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:9].Br[CH2:11][CH2:12][O:13][CH2:14][CH2:15]Br.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][C:3]=1[Cl:9]\",\"yield_000\":39.3}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":\"CCO\",\"distance\":0.0034121274948120117,\"rxn_id\":\"ord-c978110d0ebb47c5ab077decdb013eb8\",\"index\":750238,\"rxn_smiles\":\"CCO.CP(C)C.[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1.[NH4+].[OH-].c1ccncc1>>NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"procedure_details\":\"To a solution of (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 0.230 mmol) in pyridine (2 mL) was added NH4OH (200 μl) and trimethylphosphine (344 μl, 0.344 mmol) sequentially at room temperature. The reaction mixture was stirred for 2 h. After EtOH (1 mL) was added, the reaction mixture was concentrated in vacuo. The crude product was purified by flash chromatography (20% MeOH in DCM containing 0.5% NH3\\/DCM) to provide 89.6 mg of (S)\\u2014N-(2-amino-1-(3-chloro-5-fluorophenyl)ethyl)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamide (79%). LCMS (m\\/z): 488.2 (MH+), 0.66 min. 1H NMR (500 MHz, METHANOL-d4) δ ppm 7.98-7.89 (m, 1H), 7.89-7.79 (m, 1H), 7.74 (td, J=1.4, 8.0 Hz, 1H), 7.69-7.61 (m, 1H), 7.41-7.28 (m, 1H), 7.27-7.08 (m, 2H), 5.27-5.12 (m, 1H), 4.07 (dd, J=3.8, 11.0 Hz, 2H), 3.69-3.52 (m, 2H), 3.14-3.03 (m, 2H), 2.96 (tt, J=3.9, 11.7 Hz, 1H), 2.02-1.77 (m, 4H).\",\"reactant_000\":\"[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996587872505188,\"agent_000\":\"CP(C)C\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]([C:14]2[CH:35]=[CH:34][C:17]([C:18]([NH:20][C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=3)[CH2:22][N:23]=[N+]=[N-])=[O:19])=[C:16]([F:36])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[NH4+].[OH-].CP(C)C.CCO>N1C=CC=CC=1>[NH2:23][CH2:22][C@@H:21]([NH:20][C:18](=[O:19])[C:17]1[CH:34]=[CH:35][C:14]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([CH:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:4]=2)=[CH:15][C:16]=1[F:36])[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=1\",\"yield_000\":79.8},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004088282585144043,\"rxn_id\":\"ord-042249e7216a47579d0f62148c807cd2\",\"index\":714256,\"rxn_smiles\":\"C1CCOC1.C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21>>NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"procedure_details\":\"20 μL of a 1M trimethylphosphine\\/tetrahydrofuran solution was added to 6 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-azidoethyl) ester dissolved in a mixture of 0.15 mL of tetrahydrofuran and 0.02 mL of water at room temperature, and the mixture was stirred for 13 hours. After the solvent was distilled under reduced pressure, the residue was purified by reverse phase column chromatography (Wako gel 50C18 (made by Wako Pure Chemical Industries Ltd.), eluent: water to a 50% aqueous solution of acetonitrile), and the obtained solids were further washed with tetrahydrofuran, thereby yielding 2 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-aminoethyl)ester.\",\"reactant_000\":\"[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":13.0,\"reactant_003\":null,\"similarity\":0.995911717414856,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"rxn_str\":\"CP(C)C.O1CCCC1.[N:10]([CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17])=[N+]=[N-]>O1CCCC1.O>[NH2:10][CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17]\",\"yield_000\":35.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0043354034423828125,\"rxn_id\":\"ord-d978c1c7e23041a1b604dc1dd6ff7a6f\",\"index\":562746,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1>>NCc1cncc(C#Cc2ccccc2)c1\",\"procedure_details\":\"To a solution of 3-(azidomethyl)-5-(phenylethynyl)pyridine (7.8 g, 33.3 mmol) in tetrahydrofuran (101 mL) at 0° C. was added trimethylphosphine (1M in tetrahydrofuran, 49.9 mL, 49.9 mmol). After evolution of nitrogen had slowed, the ice bath was removed and stirring continued for 1 h. To this was added water (6.0 mL, 333 mmol) and the mixture stirred at room temperature for 2 h. The reaction was concentrated, dissolved in ether, washed with water (5×), then brine, dried over potassium carbonate, filtered, and concentrated to give 5.96 g (77%) as a faint yellow solid which was used without purification. 1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H)1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H). 13C NMR (CDCl3) δ: 150.8, 147.9, 137.8, 137.4, 131.8, 128.9, 128.6, 122.7, 120.3, 92.7, 86.1, 43.7. Mass spec.: 209.1 (MH)+.\",\"reactant_000\":\"[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9956645965576172,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCc1cncc(C#Cc2ccccc2)c1\",\"rxn_str\":\"[N:1]([CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[N+]=[N-].CP(C)C.O>O1CCCC1>[C:13]1([C:12]#[C:11][C:9]2[CH:10]=[C:5]([CH2:4][NH2:1])[CH:6]=[N:7][CH:8]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.005223870277404785,\"rxn_id\":\"ord-089f68b08fe543bfbdedd8c9521524ae\",\"index\":377104,\"rxn_smiles\":\"C1COCCO1.CP(C)C.O.[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21>>NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"procedure_details\":\"Azide 23 (Example 10, 100 mg, 0.23 mmol) is dissolved in 0.9 mL of 1,4-dioxane\\/H2O (8:1), and 0.3 mL of a trimethylphospine solution (1 M in THF) is added. The reaction is stirred at room temperature for 3 h, then all volatiles are removed in vacuo. The crude product is purified by flash column chromatography with dichloromethane\\/methanol (95:5 to 10:1). Yield: 87 mg (0.021 mmol, 91%).\",\"reactant_000\":\"[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9947761297225952,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"rxn_str\":\"[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][N:14]=[N+]=[N-])=[C:4]([O:17][CH2:18][C:19]2[CH:32]=[CH:31][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)[N:3]=1.CP(C)C>O1CCOCC1.O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][NH2:14])=[C:4]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:27])([F:29])[F:28])=[CH:31][CH:32]=2)[N:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.005546689033508301,\"rxn_id\":\"ord-be83b62c5d5249cf938c714d7117d666\",\"index\":193745,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1>>NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"procedure_details\":\"To a solution of (S)-2-[[1-(2-azidoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid (6.28 g, 12.11 mmol) in THF (91 mL) was added a solution of trimethylphosphine in THF (48.5 mL, 48.46 mmol, 1.0M) at 0° C. It was a clear solution in the beginning and after 30 min some precipitate was formed and this mixture was stirred for overnight at which time TLC analysis of the mixture indicated the absence of starting material. Then, 10 equiv. of water (120 mmol, 2.16 mL) was added and the mixture was stirred for 2 h at room temperature. The solvent was removed under vacuum and the residue was azeotrophed two times with toluene to give a pasty material which was purified using HPLC to obtain 4.57 g (77% yield) of (S)-2-[[1-(2-aminoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid as an amorphous white solid. ES(+)-HRMS m\\/e calcd. for C24H27Cl2N3O4 (M+H)+ 492.1452, obsd. 492.1451.\",\"reactant_000\":\"[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9944533109664917,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"rxn_str\":\"[N:1]([CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:21][CH:20]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:23][CH:24]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1\",\"yield_000\":76.6}]","literatureScore":1,"label":"TTL ALL>>167","id":167},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.9,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CS(C)=O\",\"distance\":0.004548311233520508,\"rxn_id\":\"ord-a05c1f43996841eb8a8fe4f72947522a\",\"index\":472826,\"rxn_smiles\":\"CS(C)=O.O.O=Cc1ccc(OCCCBr)cc1.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCOc1ccc(C=O)cc1\",\"procedure_details\":\"A mixture of 4-(3-bromopropyloxy)benzaldehyde (3.5 g, 14.5 mmol) and sodium azide (29 mmol, 1.9 g) in DMSO (70 ml) was stirred for 16 h, poured into water (100 ml) and extracted twice with diethyl ether. The extracts were washed with water (50 ml) and saturated aqueous sodium chloride, dried over sodium sulphate and evaporated to give a colourless oil (2.75 g). M+ 205; 360 MHz 1H n.m.r (CDCl3) 7.84 (2H, d, J 11 Hz), 7.02 (2H, d, J 11 Hz), 4.14 (2H, t, J 5.9 Hz), 3.55 (2 H, t, J 6.5 Hz), 2.09 (2 H, app. pentet, J 6.2 Hz).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=Cc1ccc(OCCCBr)cc1\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9954516887664795,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"[N-]=[N+]=NCCCOc1ccc(C=O)cc1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1.[N-:14]=[N+:15]=[N-:16].[Na+].O>CS(C)=O>[N:14]([CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1)=[N+:15]=[N-:16]\",\"yield_000\":92.4},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.005659937858581543,\"rxn_id\":\"ord-88b28baaa9a64666836fe6cd5f3479da\",\"index\":332208,\"rxn_smiles\":\"CN(C)C=O.NS(=O)(=O)c1cc2cc(CCBr)ccc2s1.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCc1ccc2sc(S(N)(=O)=O)cc2c1\",\"procedure_details\":\"Under nitrogen, a solution of 5-(2-bromoethyl)-2-sulfamoylbenzo[b]thiophene (1.2 g, 0.0037 mol), NaN3 (0.6 g, 0.0092 mol) and DMF (25 ml) was heated at 100° C. After 18 hours, the solution was cooled, poured into H2 0, and filtered to yield 0.8 g of product. The filtrate was extracted with ethyl acetate (2×). The organic layers were dried, filtered and concentrated to dryness to yield an additional 0.4 g of product (75%).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"NS(=O)(=O)c1cc2cc(CCBr)ccc2s1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9943400621414185,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"[N-]=[N+]=NCCc1ccc2sc(S(N)(=O)=O)cc2c1\",\"rxn_str\":\"Br[CH2:2][CH2:3][C:4]1[CH:16]=[CH:15][C:7]2[S:8][C:9]([S:11](=[O:14])(=[O:13])[NH2:12])=[CH:10][C:6]=2[CH:5]=1.[N-:17]=[N+:18]=[N-:19].[Na+]>CN(C=O)C>[N:17]([CH2:2][CH2:3][C:4]1[CH:16]=[CH:15][C:7]2[S:8][C:9]([S:11](=[O:14])(=[O:13])[NH2:12])=[CH:10][C:6]=2[CH:5]=1)=[N+:18]=[N-:19]\",\"yield_000\":76.6},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.006063520908355713,\"rxn_id\":\"ord-39fa152f69df4ee99d197cb3f736cb01\",\"index\":633414,\"rxn_smiles\":\"CN(C)C=O.O=C(c1ccc(Br)cc1)c1ccc(OCCCCCCBr)cc1.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCCCCOc1ccc(C(=O)c2ccc(Br)cc2)cc1\",\"procedure_details\":\"10 g of [4-(6-bromo-hexyloxy)-phenyl]-(4-bromo-phenyl)-methanone are dissolved in 200 ml of DMF and, after the addition of 14.7 g of sodium azide, the mixture is stirred at 90° C. for 24 hours, filtered and the filtrates are concentrated under reduced pressure. The residue is taken up in 200 ml of ethyl acetate and washed with 10% aqueous sodium hydrogen carbonate solution. The organic phase is dried and concentrated. There are obtained 9.2 9 of [4-(6-azido-hexyloxy)-phenyl]-(4-bromo-phenyl)-methanone, MS: m\\/e 401 (M+H+, 1Br).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=C(c1ccc(Br)cc1)c1ccc(OCCCCCCBr)cc1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9939364790916443,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCCCCCOc1ccc(C(=O)c2ccc(Br)cc2)cc1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=2)=[O:16])=[CH:11][CH:10]=1.[N-:24]=[N+:25]=[N-:26].[Na+]>CN(C=O)C>[N:24]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=2)=[O:16])=[CH:11][CH:10]=1)=[N+:25]=[N-:26]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":\"O\",\"distance\":0.00608062744140625,\"rxn_id\":\"ord-c920b47a9c854e79bef436db81ec47e9\",\"index\":208626,\"rxn_smiles\":\"CCO.O.O.O=C(C1Cc2ccc(OCCCBr)cc21)N1CCCCC1.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCOc1ccc2c(c1)C(C(=O)N1CCCCC1)C2\",\"procedure_details\":\"Sodium azide (2.4 g) is added to a stirred solution of 5-(3-bromopropoxy)-1-(1-piperidinylcarbonyl)benzocyclobutene (12.8 g) in ethanol\\/water (13 ml\\/130 ml). The reaction mixture is refluxed overnight, poured into water, washed with methylene chloride and the organic extract washed, dried, filtered and evaporated in vacuo affording the desired azide product as an oil, which is used in the next step without further purification.\",\"reactant_000\":\"O=C(C1Cc2ccc(OCCCBr)cc21)N1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9939193725585938,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"[N-]=[N+]=NCCCOc1ccc2c(c1)C(C(=O)N1CCCCC1)C2\",\"rxn_str\":\"[N-:1]=[N+:2]=[N-:3].[Na+].Br[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[CH:15]([C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:17])[CH2:14][C:13]2=[CH:24][CH:25]=1.O>C(O)C.O>[N:1]([CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[CH:15]([C:16]([N:18]3[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)=[O:17])[CH2:14][C:13]2=[CH:24][CH:25]=1)=[N+:2]=[N-:3]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"CCOC(C)=O\",\"distance\":0.006417810916900635,\"rxn_id\":\"ord-32d3265547f4410489e589382cdf38e2\",\"index\":725970,\"rxn_smiles\":\"CCOC(C)=O.CS(C)=O.O=C(O)c1cc(N=Nc2ccc(OCCCCCCCCBr)cc2)ccc1O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCCCCCCOc1ccc(N=Nc2ccc(O)c(C(=O)O)c2)cc1\",\"procedure_details\":\"5-((4-(8-Bromooctyloxy)phenyl)diazenyl)-2-hydroxybenzoic acid (2.50 g, 5.6 mmol) was dissolved in DMSO (40 mL) and NaN3 (1.10 g, 16.9 mmol) was added slowly to the reaction mixture with stirring at room temperature. After 48 h, the mixture was diluted with EtOAc (100 mL), washed with water (4×20 mL), brine (20 mL), dried over Na2SO4, and filtered. Volatiles were removed in vacuo and the residue subjected to column chromatography on silica gel 60 (230-400 mesh) using EtOAc and methanol (98:2) as the elutant to give 2.10 g (5.1 mmol, 91%) of the product as a red-brown solid, mp 54-56° C. 1H NMR (500 MHz, CDCl3) δ 1.27-1.58 (m, 8H), 1.62-1.64 (m, 2H), 1.81-1.86 (m, 2H), 3.31 (t, J=5 Hz, 2H), 4.06 (t, J=6.5 Hz, 2H), 6.88-7.01 (m, 3H), 7.84 (d, J=10 Hz, 2H), 7.91 (dd, J=15 Hz, 2.5 Hz, 1H), 8.47 (d, J=2.5 Hz, 1H); 13C NMR (125 MHz, CDCl3+CD3OD) δ 22.0, 25.3, 25.4, 28.5, 28.6, 28.8, 31.2, 50.8, 67.7, 114.1, 116.5, 117.5, 123.6, 126.2, 144.6, 146.2, 160.7, 175.0; HRMS (ESI) calculated for C21H26N5O4 (M+H)+412.1979, observed 412.1971.\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=C(O)c1cc(N=Nc2ccc(OCCCCCCCCBr)cc2)ccc1O\",\"rxn_time\":48.0,\"reactant_003\":null,\"similarity\":0.9935821890830994,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"[N-]=[N+]=NCCCCCCCCOc1ccc(N=Nc2ccc(O)c(C(=O)O)c2)cc1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]=[N:18][C:19]2[CH:20]=[CH:21][C:22]([OH:28])=[C:23]([CH:27]=2)[C:24]([OH:26])=[O:25])=[CH:13][CH:12]=1.[N-:29]=[N+:30]=[N-:31].[Na+]>CS(C)=O.CCOC(C)=O>[N:29]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]=[N:18][C:19]2[CH:20]=[CH:21][C:22]([OH:28])=[C:23]([CH:27]=2)[C:24]([OH:26])=[O:25])=[CH:13][CH:12]=1)=[N+:30]=[N-:31]\",\"yield_000\":91.1}]","literatureScore":1,"label":"ER UA TTL ALL>>672","id":672},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":121}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":121}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":121}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":121}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.14,"id":164,"pathId":121}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":5,"reaction":{"label":"TTL ALL>>987","id":987},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"IVRMZWNICZWHMI","smiles":"[N-]=[N+]=[N-]","intrinsicScore":0.051,"id":987,"pathId":121}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"FCEJYNJLOZLCCR","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1OCCCN=[N+]=[N-]","intrinsicScore":0.3,"id":672,"pathId":121}],"RXN":"[cH:26]1[cH:25][c:24]([c:23]([cH:22][c:21]1[NH:20][c:19]2[c:14]3[cH:13][c:9]([c:8]([cH:29][c:15]3[n:16][cH:17][n:18]2)[O:7][CH2:6][CH2:5][CH2:4]Br)[N+:10](=[O:11])[O-:12])[Cl:28])[F:27].[N-:2]=[N+:1]=[N-:3]>>[cH:26]1[cH:25][c:24]([c:23]([cH:22][c:21]1[NH:20][c:19]2[c:14]3[cH:13][c:9]([c:8]([cH:29][c:15]3[n:16][cH:17][n:18]2)[O:7][CH2:6][CH2:5][CH2:4][N:2]=[N+:1]=[N-:3])[N+:10](=[O:11])[O-:12])[Cl:28])[F:27];9.7.23;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NGGHYTSBRHGJPA","smiles":"NCCCOC1=C(C=C2C(NC3=CC=C(F)C(Cl)=C3)=NC=NC2=C1)[N+]([O-])=O","intrinsicScore":0.051,"id":167,"pathId":121}],"RXN":"[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][N:20]=[N+]=[N-])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27]>C1CCOC1.C(OCC)(C)=O.CP(C)C.O>[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][NH2:20])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27];9.7.13;Azido"},{"depth":3,"reaction":{"label":"TTL ALL>>51","id":51},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"FOZVXADQAHVUSV","smiles":"BrCCOCCBr","intrinsicScore":0.051,"id":51,"pathId":121}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":121}],"RXN":"[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][NH2:8])[N+:30](=[O:31])[O-:32])[Cl:29])[F:26].[CH2:2]([CH2:1]Br)[O:3][CH2:4][CH2:5]Br>N#CC.[O-]C(=O)[O-].[I-].[K+]>[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][N:8]4[CH2:1][CH2:2][O:3][CH2:4][CH2:5]4)[N+:30](=[O:31])[O-:32])[Cl:29])[F:26];4.2.5;Morpholine"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":121}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":121}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":121}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.033","depth":0,"reaction":{"label":">>0","id":0,"pathId":317},"children":[{"depth":1,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":317}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":317}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":317}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":317}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":317}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":317}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":317}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":317}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":317}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":317}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":317}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":317}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":317}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.035","depth":0,"reaction":{"label":">>0","id":0,"pathId":853},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.6,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.008023500442504883,\"rxn_id\":\"ord-42dc5bd007e148f297483fd574a84112\",\"index\":514864,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCN(CC)CC.Cl.Cl.N#Cc1ccc(Cn2cncc2CCN)cc1F>>N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride (0.92 g, 0.0029 mmol) in acetonitrile (150 mL) and triethylamine (3.2 mL) was added 2-bromoethyl ether (0.839 mL, 0.0067 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in uacuo and the residue was dissolved in EtOAc which was washed twice with 1M HCl (100 mL). The HCl layers were combined and adjusted to pH=9 with solid Na2CO3 and extraxcted 3 times with EtOAc. The EtOAc layers were combined and dried with brine and MgSO4. Removal of the EtOAc in vacuo yielded the title compound which was used as is in the next step.\",\"reactant_000\":\"N#Cc1ccc(Cn2cncc2CCN)cc1F\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919764995574951,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=2)[CH:9]=[N:8][CH:7]=1.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>C(#N)C.C(N(CC)CC)C>[F:20][C:14]1[CH:13]=[C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][N:3]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:7][N:8]=[CH:9]2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.008291244506835938,\"rxn_id\":\"ord-08bb54aa0ab244ff90317c31f9d4c5e8\",\"index\":731783,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.NC1CCN(Cc2ccccc2)CC1.O=C([O-])[O-].[K+].[K+]>>c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"procedure_details\":\"To a stirred mixture of 4-amino-1-benzylpiperidine (1.53 mL, 7.5 mmol), K2CO3 (2.28 g, 16.5 mmol) and DMF (15 mL) heated at 50° C. was added dropwise over 60 min bis(2-bromoethyl) ether (0.96 mL, 7.65 mmol). After stirring for 6 hours at 80° C., the solvent was removed by blowing with a stream of nitrogen over 2 hours. The residue was purified on a silica gel column to give 1.7 g (87%) of 4-(1-benzyl-piperidin-4-yl)morpholine as a waxy solid.\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"NC1CCN(Cc2ccccc2)CC1\",\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9917087554931641,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"rxn_str\":\"[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>CN(C=O)C>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:1]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1\",\"yield_000\":87.1},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.008305191993713379,\"rxn_id\":\"ord-ac7a693c46694fd5b13039f5c104d79e\",\"index\":134482,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N.O=C([O-])[O-].[K+].[K+]>>CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"procedure_details\":\"cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane\\/methanol\\/ammonia 100:0:0->140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m\\/e=403.3 [(M+H)+].\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9916948080062866,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"rxn_str\":\"[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]\",\"yield_000\":68.6},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.00859677791595459,\"rxn_id\":\"ord-aa3eb88c8e6c445794e16d41429514f0\",\"index\":719114,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O.CCN(CC)CC.Cl.Cl>>CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-2-methyl-imidazol-1-ylmethyl]-2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile dihydrochloride (as described in Example 11) (0.25 g, 0.456 mmol) in acetonitrile (35.0 mL) and triethylamine (1.8 mL) was added 2-bromoethyl ether (0.133 mL, 1.06 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in vacuo to obtain the title compound after purification by preparative HPLC.\",\"reactant_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9914032220840454,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]4([CH2:36][CH3:37])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]4=[O:35])[CH:22]=3)[CH:13]=2)[C:9]([CH3:38])=[N:8][CH:7]=1.Br[CH2:40][CH2:41][O:42][CH2:43][CH2:44]Br>C(#N)C.C(N(CC)CC)C>[CH2:36]([C:27]1([C:23]2[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=2)[O:20][C:14]2[CH:13]=[C:12]([CH2:11][N:10]3[C:6]([CH2:5][CH2:4][N:3]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[CH:7][N:8]=[C:9]3[CH3:38])[CH:19]=[CH:18][C:15]=2[C:16]#[N:17])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]1=[O:35])[CH3:37]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.008690357208251953,\"rxn_id\":\"ord-90e436a959164d40ab8c094946564425\",\"index\":740936,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.Nc1ccc(Br)c(Cl)c1.O.O=C([O-])[O-].[I-].[K+].[K+].[K+]>>Clc1cc(N2CCOCC2)ccc1Br\",\"procedure_details\":\"4-Bromo-3-chloroaniline (500 mg) was dissolved in DMF (10 ml), and bis(2-bromoethyl)ether (1.12 g), K2CO3 (1.34 g), and potassium iodide (80 mg) were added thereto, followed by stirring at 80° C. for 2 days. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 20% EtOAc\\/hexane) to obtain 4-(4-bromo-3-chlorophenyl)morpholine (263 mg).\",\"reactant_000\":\"Nc1ccc(Br)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":48.0,\"reactant_003\":null,\"similarity\":0.991309642791748,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[I-]\",\"agent_002\":\"[K+]\",\"temperature\":80.0,\"product_000\":\"Clc1cc(N2CCOCC2)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:9].Br[CH2:11][CH2:12][O:13][CH2:14][CH2:15]Br.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][C:3]=1[Cl:9]\",\"yield_000\":39.3}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":\"CCO\",\"distance\":0.0034121274948120117,\"rxn_id\":\"ord-c978110d0ebb47c5ab077decdb013eb8\",\"index\":750238,\"rxn_smiles\":\"CCO.CP(C)C.[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1.[NH4+].[OH-].c1ccncc1>>NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"procedure_details\":\"To a solution of (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 0.230 mmol) in pyridine (2 mL) was added NH4OH (200 μl) and trimethylphosphine (344 μl, 0.344 mmol) sequentially at room temperature. The reaction mixture was stirred for 2 h. After EtOH (1 mL) was added, the reaction mixture was concentrated in vacuo. The crude product was purified by flash chromatography (20% MeOH in DCM containing 0.5% NH3\\/DCM) to provide 89.6 mg of (S)\\u2014N-(2-amino-1-(3-chloro-5-fluorophenyl)ethyl)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamide (79%). LCMS (m\\/z): 488.2 (MH+), 0.66 min. 1H NMR (500 MHz, METHANOL-d4) δ ppm 7.98-7.89 (m, 1H), 7.89-7.79 (m, 1H), 7.74 (td, J=1.4, 8.0 Hz, 1H), 7.69-7.61 (m, 1H), 7.41-7.28 (m, 1H), 7.27-7.08 (m, 2H), 5.27-5.12 (m, 1H), 4.07 (dd, J=3.8, 11.0 Hz, 2H), 3.69-3.52 (m, 2H), 3.14-3.03 (m, 2H), 2.96 (tt, J=3.9, 11.7 Hz, 1H), 2.02-1.77 (m, 4H).\",\"reactant_000\":\"[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996587872505188,\"agent_000\":\"CP(C)C\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]([C:14]2[CH:35]=[CH:34][C:17]([C:18]([NH:20][C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=3)[CH2:22][N:23]=[N+]=[N-])=[O:19])=[C:16]([F:36])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[NH4+].[OH-].CP(C)C.CCO>N1C=CC=CC=1>[NH2:23][CH2:22][C@@H:21]([NH:20][C:18](=[O:19])[C:17]1[CH:34]=[CH:35][C:14]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([CH:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:4]=2)=[CH:15][C:16]=1[F:36])[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=1\",\"yield_000\":79.8},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004088282585144043,\"rxn_id\":\"ord-042249e7216a47579d0f62148c807cd2\",\"index\":714256,\"rxn_smiles\":\"C1CCOC1.C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21>>NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"procedure_details\":\"20 μL of a 1M trimethylphosphine\\/tetrahydrofuran solution was added to 6 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-azidoethyl) ester dissolved in a mixture of 0.15 mL of tetrahydrofuran and 0.02 mL of water at room temperature, and the mixture was stirred for 13 hours. After the solvent was distilled under reduced pressure, the residue was purified by reverse phase column chromatography (Wako gel 50C18 (made by Wako Pure Chemical Industries Ltd.), eluent: water to a 50% aqueous solution of acetonitrile), and the obtained solids were further washed with tetrahydrofuran, thereby yielding 2 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-aminoethyl)ester.\",\"reactant_000\":\"[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":13.0,\"reactant_003\":null,\"similarity\":0.995911717414856,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"rxn_str\":\"CP(C)C.O1CCCC1.[N:10]([CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17])=[N+]=[N-]>O1CCCC1.O>[NH2:10][CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17]\",\"yield_000\":35.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0043354034423828125,\"rxn_id\":\"ord-d978c1c7e23041a1b604dc1dd6ff7a6f\",\"index\":562746,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1>>NCc1cncc(C#Cc2ccccc2)c1\",\"procedure_details\":\"To a solution of 3-(azidomethyl)-5-(phenylethynyl)pyridine (7.8 g, 33.3 mmol) in tetrahydrofuran (101 mL) at 0° C. was added trimethylphosphine (1M in tetrahydrofuran, 49.9 mL, 49.9 mmol). After evolution of nitrogen had slowed, the ice bath was removed and stirring continued for 1 h. To this was added water (6.0 mL, 333 mmol) and the mixture stirred at room temperature for 2 h. The reaction was concentrated, dissolved in ether, washed with water (5×), then brine, dried over potassium carbonate, filtered, and concentrated to give 5.96 g (77%) as a faint yellow solid which was used without purification. 1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H)1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H). 13C NMR (CDCl3) δ: 150.8, 147.9, 137.8, 137.4, 131.8, 128.9, 128.6, 122.7, 120.3, 92.7, 86.1, 43.7. Mass spec.: 209.1 (MH)+.\",\"reactant_000\":\"[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9956645965576172,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCc1cncc(C#Cc2ccccc2)c1\",\"rxn_str\":\"[N:1]([CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[N+]=[N-].CP(C)C.O>O1CCCC1>[C:13]1([C:12]#[C:11][C:9]2[CH:10]=[C:5]([CH2:4][NH2:1])[CH:6]=[N:7][CH:8]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.005223870277404785,\"rxn_id\":\"ord-089f68b08fe543bfbdedd8c9521524ae\",\"index\":377104,\"rxn_smiles\":\"C1COCCO1.CP(C)C.O.[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21>>NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"procedure_details\":\"Azide 23 (Example 10, 100 mg, 0.23 mmol) is dissolved in 0.9 mL of 1,4-dioxane\\/H2O (8:1), and 0.3 mL of a trimethylphospine solution (1 M in THF) is added. The reaction is stirred at room temperature for 3 h, then all volatiles are removed in vacuo. The crude product is purified by flash column chromatography with dichloromethane\\/methanol (95:5 to 10:1). Yield: 87 mg (0.021 mmol, 91%).\",\"reactant_000\":\"[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9947761297225952,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"rxn_str\":\"[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][N:14]=[N+]=[N-])=[C:4]([O:17][CH2:18][C:19]2[CH:32]=[CH:31][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)[N:3]=1.CP(C)C>O1CCOCC1.O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][NH2:14])=[C:4]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:27])([F:29])[F:28])=[CH:31][CH:32]=2)[N:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.005546689033508301,\"rxn_id\":\"ord-be83b62c5d5249cf938c714d7117d666\",\"index\":193745,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1>>NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"procedure_details\":\"To a solution of (S)-2-[[1-(2-azidoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid (6.28 g, 12.11 mmol) in THF (91 mL) was added a solution of trimethylphosphine in THF (48.5 mL, 48.46 mmol, 1.0M) at 0° C. It was a clear solution in the beginning and after 30 min some precipitate was formed and this mixture was stirred for overnight at which time TLC analysis of the mixture indicated the absence of starting material. Then, 10 equiv. of water (120 mmol, 2.16 mL) was added and the mixture was stirred for 2 h at room temperature. The solvent was removed under vacuum and the residue was azeotrophed two times with toluene to give a pasty material which was purified using HPLC to obtain 4.57 g (77% yield) of (S)-2-[[1-(2-aminoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid as an amorphous white solid. ES(+)-HRMS m\\/e calcd. for C24H27Cl2N3O4 (M+H)+ 492.1452, obsd. 492.1451.\",\"reactant_000\":\"[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9944533109664917,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"rxn_str\":\"[N:1]([CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:21][CH:20]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:23][CH:24]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1\",\"yield_000\":76.6}]","literatureScore":1,"label":"TTL ALL>>167","id":167},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008967578411102295,\"rxn_id\":\"ord-cf2e4e3955c04b01a2130e020e40723c\",\"index\":264007,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-4-fluorophenylamine (1.67 g, 4.87 mmoles) and sodium azide (0.38 g, 5.84 mmoles) in DMSO (20 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (1.44 g, 4.14 mmoles).\",\"reactant_000\":\"Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9910324215888977,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([O:18][CH2:19][CH2:20]Cl)[C:12]=2[NH2:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>CS(C)=O.O>[N:23]([CH2:20][CH2:19][O:18][C:13]1[CH:14]=[C:15]([F:17])[CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:22])=[N+:24]=[N-:25]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CCOC(C)=O\",\"distance\":0.00959622859954834,\"rxn_id\":\"ord-693a2494d2a64d6e84f87595007867e9\",\"index\":765833,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc(OCCCCl)cc1CO.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"procedure_details\":\"DMF (7.5 mL) was added to (5-(3-chloropropoxy)-2-nitrophenyl)methanol (635 mg, 0.00258 moles) and sodium azide (252 mg, 0.00387 moles) in a flask, and the resulting mixture was heated to 70° C. and stirred overnight. The reaction was diluted in ethyl acetate (100 mL) and washed twice with water (75 mL each) and once with brine (75 mL). The organic layer was dried with anhydrous magnesium sulfate, which was filtered out. The filtrate was concentrated on a rotary evaporator and dried in vacuo overnight to yield (5-(3-azidopropoxy)-2-nitrophenyl)methanol as a yellow solid (yield 88%). H NMR (400 MHz, CD2Cl2) δ 8.16 (d, J=9.1 Hz, 1H), 7.27 (d, J=2.8 Hz, 1H), 6.91 (dd, J=9.1, 2.8 Hz, 1H), 4.98 (s, 2H), 4.18 (t, J=6.0 Hz, 2H), 3.53 (t, J=6.6 Hz, 2H), 2.12-2.06 (m, 2H). 13C-NMR (100 MHz, CD2Cl2) δ 163.99, 141.22, 128.43, 114.97, 113.93, 66.15, 63.26, 48.68, 29.13 HRMS m\\/z: calculated for C10H12N4O4 [M+H]+, 253.0931. found, 253.0939.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCCCCl)cc1CO\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9904037714004517,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"rxn_str\":\"CN(C=O)C.Cl[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>C(OCC)(=O)C>[N:22]([CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1)=[N+:23]=[N-:24]\",\"yield_000\":88.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CS(C)=O\",\"distance\":0.009707868099212646,\"rxn_id\":\"ord-ed6541dc83464b24a92f34950c9068d0\",\"index\":137604,\"rxn_smiles\":\"CS(C)=O.O.O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"procedure_details\":\"A mixture of 6-(2-chloro-ethoxy)-3-(naphthalene-1-sulfonyl)-1-H-indazole (0.19 g, 0.5 mmoles) and sodium azide (0.04 g, 0.62 mmoles) in DMSO (2 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.17 g, 0.45 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9902921319007874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1.[N-:27]=[N+:28]=[N-:29].[Na+]>CS(C)=O.O>[N:27]([CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1)=[N+:28]=[N-:29]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.010035336017608643,\"rxn_id\":\"ord-dc8e8747d9b6443687f6f629e49ca7d3\",\"index\":120480,\"rxn_smiles\":\"CN(C)C=O.Nc1ncnc2c1ncn2CCCCl.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"procedure_details\":\"A mixture of 9-(3-chloropropyl)adenine and sodium azide in DMF was stirred at 80° C. for 24 hours, cooled to room temperature and filtered. The solid was washed with CH2Cl2. The solvent was removed from the combined filtrates and the residue was taken up in water with sonication. The aqueous layer was extracted with CH2Cl2. After removing the solvent, the crude product was recrystallized from ethanol to give 9-(3-azidopropyl)adenine as a white crystalline solid.\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1ncnc2c1ncn2CCCCl\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9899646639823914,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14].[N-:15]=[N+:16]=[N-:17].[Na+]>CN(C=O)C>[N:15]([CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14])=[N+:16]=[N-:17]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.010115861892700195,\"rxn_id\":\"ord-5c4de244180f41a2bbc87a484238a728\",\"index\":335449,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-phenylamine (0.5 g, 1.53 mmoles) and sodium azide (0.15 g, 2.29 mmoles) in DMSO (10 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.39 g, 1.17 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9898841381072998,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19]Cl)[C:12]=2[NH2:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>CS(C)=O.O>[N:22]([CH2:19][CH2:18][O:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:21])=[N+:23]=[N-:24]\",\"yield_000\":null}]","literatureScore":0.99,"label":"ER UA TTL ALL>>672","id":672},"children":[{"depth":6,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":7,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":8,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":853}]},{"depth":8,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":853}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":7,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.6,"id":165,"pathId":853}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":6,"reaction":{"label":"AT T5 ER UA TTL ALL>>990","id":990},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"JUINSXZKUKVTMD","smiles":"N=[N+]=[N-]","intrinsicScore":0.6,"id":990,"pathId":853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"FCEJYNJLOZLCCR","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1OCCCN=[N+]=[N-]","intrinsicScore":0.3,"id":672,"pathId":853}],"RXN":"[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4]Cl)[N+:27](=[O:28])[O-:29])[Cl:24])[F:21].[NH:3]=[N+:1]=[N-:2]>>[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4][N:3]=[N+:1]=[N-:2])[N+:27](=[O:28])[O-:29])[Cl:24])[F:21];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NGGHYTSBRHGJPA","smiles":"NCCCOC1=C(C=C2C(NC3=CC=C(F)C(Cl)=C3)=NC=NC2=C1)[N+]([O-])=O","intrinsicScore":0.051,"id":167,"pathId":853}],"RXN":"[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][N:20]=[N+]=[N-])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27]>C1CCOC1.C(OCC)(C)=O.CP(C)C.O>[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][NH2:20])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27];9.7.13;Azido"},{"depth":4,"reaction":{"label":"TTL ALL>>51","id":51},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"FOZVXADQAHVUSV","smiles":"BrCCOCCBr","intrinsicScore":0.051,"id":51,"pathId":853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":853}],"RXN":"[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][NH2:8])[N+:30](=[O:31])[O-:32])[Cl:29])[F:26].[CH2:2]([CH2:1]Br)[O:3][CH2:4][CH2:5]Br>N#CC.[O-]C(=O)[O-].[I-].[K+]>[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][N:8]4[CH2:1][CH2:2][O:3][CH2:4][CH2:5]4)[N+:30](=[O:31])[O-:32])[Cl:29])[F:26];4.2.5;Morpholine"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":853}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":853}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":853}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":853}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.07","depth":0,"reaction":{"label":">>0","id":0,"pathId":297},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004968404769897461,\"rxn_id\":\"ord-67cd89c92ec043eaa8c192a52c6055e1\",\"index\":71209,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)c(F)c2)cc1>>N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"procedure_details\":\"The product from Example 167A and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (99% yield). 1HNMR (300 MHz, CDCl3) δ2.30 (m, 2H), 3.80 (m, 2H), 4.25 (m, 2H), 7.12-7.75 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)c(F)c2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950315952301025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)=[CH:3][C:2]=1[F:1]\",\"yield_000\":99.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005435526371002197,\"rxn_id\":\"ord-593d5907c892416383020940bf139801\",\"index\":592545,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)cc2)cc1F>>N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"procedure_details\":\"The product from Example 166B and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (98% yield). 1HNMR (300 MHz, CDCl3) δ2.25 (m, 2H), 3.80 (m, 2H), 4.20 (m, 2H), 7.00-7.65 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)cc2)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945644736289978,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([F:1])[CH:3]=2)=[CH:11][CH:12]=1\",\"yield_000\":98.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005583524703979492,\"rxn_id\":\"ord-f2089ee29c9c49d6bda509b96fde9e15\",\"index\":355059,\"rxn_smiles\":\"ClCCCBr.Cn1ncc(-c2ccc(O)cc2)cc1=O>>Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"procedure_details\":\"5-[4-(3-Chloro-propoxy)-phenyl]-2-methyl-2H-pyridazin-3-one was prepared from 5-(4-hydroxy-phenyl)-2-methyl-2H-pyridazin-3-one with 1-bromo-3-chloro-propane using the procedure described in Example 86 Step 3; Mp 90-91° C.; MS m\\/z 279 (M+H).\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"Cn1ncc(-c2ccc(O)cc2)cc1=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944164752960205,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0058318376541137695,\"rxn_id\":\"ord-0943760d2d71451cb76c1188d0d02866\",\"index\":410217,\"rxn_smiles\":\"ClCCCBr.O=C1NCCn2c1cc1cc(O)cnc12>>O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"procedure_details\":\"The title compound was synthesized in analogy to example 2, intermediate, from 7-hydroxy-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one (example 84, intermediate a) and 1-bromo-3-chloropropane, to give the desired product as a light yellow solid (80%).\",\"reactant_000\":\"O=C1NCCn2c1cc1cc(O)cnc12\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941681623458862,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"rxn_str\":\"[OH:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1\",\"yield_000\":80.0},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.006563842296600342,\"rxn_id\":\"ord-cbbf3a06c7d04efaab9b011975b2bcaf\",\"index\":118810,\"rxn_smiles\":\"CC(C)=O.ClCCCBr.O=C1CSc2cc(O)ccc2N1>>O=C1CSc2cc(OCCCCl)ccc2N1\",\"procedure_details\":\"After a mixture consisting of 7-hydroxy-3,4-dihydro-2H-1,4-benzothiazin-3-one (1.812 g, 10 mmol), 1bromo-3-chloropropane (2.362 g, 15 mmol), potassium carbate (4.146 g, 30 mmol) and acetone (40 mmol) was heated under reflux and stirring for 24 hours, insolube matter was filtered off, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel column (developer: chloroform) to purify the same, and was then recrystallized from acetone. The title compound (1.300 g) was obtained as yellow leaflets (yield: 50.4%).\",\"reactant_000\":\"O=C1CSc2cc(O)ccc2N1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9934361577033997,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CSc2cc(OCCCCl)ccc2N1\",\"rxn_str\":\"[OH:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.Br[CH2:14][CH2:15][CH2:16][Cl:17].CC(C)=O>>[Cl:17][CH2:16][CH2:15][CH2:14][O:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1\",\"yield_000\":50.4}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":297}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":297}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":297}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":297}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.43,"id":154,"pathId":297}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":4,"reaction":{"label":"TTL ALL T5 UA ER ALL>>90","id":90},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MFESCIUQSIBMSM","smiles":"ClCCCBr","intrinsicScore":0.43,"id":90,"pathId":297}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":297}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:26]([CH2:25][Cl:24])[CH2:27]Br>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:23][CH2:27][CH2:26][CH2:25][Cl:24])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.9;Williamson"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":297}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":297}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":297}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":297}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":297}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.216","depth":0,"reaction":{"label":">>0","id":0,"pathId":768},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.005186200141906738,\"rxn_id\":\"ord-d1fa20d56e464afca9b17e9c52f114e7\",\"index\":450278,\"rxn_smiles\":\"CCCCO.CCOC(=O)c1ccc(-c2cc3c(Cl)ncnc3[nH]2)cc1.Nc1ccc(F)c(Cl)c1>>CCOC(=O)c1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3[nH]2)cc1\",\"procedure_details\":\"3.6 g (12 mmol) 4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-benzoic acid ethyl ester (WO 97\\/02266) are suspended in 80 ml n-butanol and treated with 3.5 g (24 mmol) 3-chloro-4-fluoro-aniline. The mixture is heated to 145° C. under stirring. After 30 min a clear brown solution is obtained which turns into a thick suspension after 2 h. After a total of 3 h the reaction mixture is cooled in an ice bath and the product collected by filtration; m.p.>300° C.; Rf(dichloromethane\\/ethanol 95:5 plus 1% conc. ammonia)=0.29; HPLC tR=11.66 min.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1ccc(-c2cc3c(Cl)ncnc3[nH]2)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9948137998580933,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":145.0,\"product_000\":\"CCOC(=O)c1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3[nH]2)cc1\",\"rxn_str\":\"[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:14]3[N:15]=[CH:16][N:17]=[C:18](Cl)[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)[CH3:2].[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>C(O)CCC>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:26][C:25]4[CH:27]=[CH:28][C:29]([F:30])=[C:23]([Cl:22])[CH:24]=4)[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.005290091037750244,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947099089622498,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"CC(C)(C)O\",\"distance\":0.0053021907806396484,\"rxn_id\":\"ord-5510c71cc19244ccb4d87f14f34e8de5\",\"index\":424079,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"procedure_details\":\"To a solution of 4-chloro-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine (40 mg, 0.15 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 1 ml) was added 3-chloro-4-fluoroaniline (22 mg, 0.15 mmol). The mixture was heated at 90° C. for 2 days. After cooling down to room temperature, the solvents were removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 100:1) to yield the title compound as a white solid (28 mg, 50%).\",\"reactant_000\":\"Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9946978092193604,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[CH:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":49.9},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.005939364433288574,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9940606355667114,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.006047487258911133,\"rxn_id\":\"ord-110ea862e79f4175b380aaf2573b8840\",\"index\":333623,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Cl)c12.CCN(C(C)C)C(C)C.Nc1ccc(F)c(Cl)c1>>CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Nc3ccc(F)c(Cl)c3)c12\",\"procedure_details\":\"The crude tert-butyl (2R)-2-({[7-(benzyloxy)-4-chloroquinazolin-5-yl]oxy}methyl)-pyrrolidine-1-carboxylate was taken up in THF (5 ml) and 3-chloro-4-fluoroaniline (160 mg) and N,N-diisopropylethylamine (580 μl) were each added in one portion and the solution was heated at 70° C. for 18 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo to leave a thick brown oil. Purification by flash chromatography, using 1.5% methanol in DCM as eluent, gave the tert-butyl (2R)-2-[({7-(benzyloxy)-4-[3-chloro-4-fluoroanilino]quinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate as a beige foam (350 mg, 54% over 2 steps); Mass spectrum MH+ 481.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Cl)c12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9939525127410889,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cc(OCc2ccccc2)cc2ncnc(Nc3ccc(F)c(Cl)c3)c12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](Cl)=[N:14][CH:15]=[N:16]2)=[C:11]([O:20][CH2:21][C@H:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:34][C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][C:41]=1[F:42])[NH2:38].C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:38][C:37]3[CH:39]=[CH:40][C:41]([F:42])=[C:35]([Cl:34])[CH:36]=3)=[N:14][CH:15]=[N:16]2)=[C:11]([O:20][CH2:21][C@H:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0024016499519348145,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9975983500480652,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0034421682357788086,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9965578317642212,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005340635776519775,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9946593642234802,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005926012992858887,\"rxn_id\":\"ord-61db4d46573641b09a365452241e4a72\",\"index\":23563,\"rxn_smiles\":\"C1CCOC1.CCc1nc2cc(F)ccc2[n+]([O-])n1.O.OCCCN1CCOCC1.[H-].[Na+]>>CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"procedure_details\":\"NaH (60% dispersion in oil, 310 mg, 7.75 mmol) was added to dry THF (10 mL) and stirred at 20° C. for 20 min prior to the addition of 3-(4-morpholinyl)propanol (676 mg, 4.66 mmol). The mixture was stirred for 30 min, fluoride 28 (300 mg, 1.55 mmol) added and the resulting solution stirred at 20° C. for 2.5 h under N2. Water was added and the solution extracted with DCM (4×30 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by column chromatography, eluting with a gradient (0-5%) MeOH\\/DCM to give 1-oxide 31 (257 mg, 52%) as a pale yellow solid, mp 108-111° C.; 1H NMR δ 8.33 (d, J=9.3 Hz, 1 H, H-8), 7.21-7.26 (m, 2 H, H-7 and H-5), 4.22 (t, J=6.4 Hz, 2 H, CH2), 3.73 (t, J=4.6 Hz, 4 H, 2×CH2O), 3.00 (q, J=7.6 Hz, 2 H, CH2), 2.55 (t, J=7.0 Hz, 2 H, CH2), 2.48 (t, J=4.6 Hz, 4 H, 2×CH2N), 2.06 (m, 2 H, CH2), 1.43 (t, J=7.6 Hz, 3 H, CH3); 13C NMR δ 168.7, 164.6, 150.3, 128.4, 123.1, 121.6, 106.3, 67.3 (2), 66.9, 55.1, 53.7 (2), 30.7, 26.0, 12.2. Anal. Calcd for C16H22N4O3: C, 60.4; H, 7.0; N, 17.6. Found: C, 60.4; H, 7.0; N, 17.4%.\",\"reactant_000\":\"CCc1nc2cc(F)ccc2[n+]([O-])n1\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9940739870071411,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"rxn_str\":\"[H-].[Na+].C1COCC1.[N:8]1([CH2:14][CH2:15][CH2:16][OH:17])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27](F)=[CH:26][C:24]=2[N:25]=1)[CH3:19]>O>[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27]([O:17][CH2:16][CH2:15][CH2:14][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:26][C:24]=2[N:25]=1)[CH3:19]\",\"yield_000\":52.1},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005959570407867432,\"rxn_id\":\"ord-a73cb883fae1487ca599634bf5ed7e4b\",\"index\":602333,\"rxn_smiles\":\"C1CCOC1.NS(=O)(=O)c1ncccc1F.OCCF.[H-].[Na+]>>NS(=O)(=O)c1ncccc1OCCF\",\"procedure_details\":\"5.76 ml of 2-fluoroethanol are added dropwise, with cooling, to a suspension of 6.54 g of sodium hydride (55.6% NaH in oil) in 120 ml of tetrahydrofuran so that the temperature does not exceed 20° C. When the dropwise addition is complete, the reaction mixture is stirred at room temperature for 15 minutes and then a further solution of 10.56 g of 3-fluoro-pyrid-2-ylsulfonamide in 60 ml of tetrahydrofuran is added dropwise over a period of 10 minutes. The reaction solution is then stirred for 10 minutes at room temperature and for 2 hours at reflux before it is cooled and concentrated. For purification, the oil remaining is chromatographed on a silica gel column using ethyl acetate\\/hexane 4\\/1. Evaporation of the eluant yields a light-coloured oil which crystallises spontaneously, yielding 5.88 g of title product which melts at 122°-123° C.\",\"reactant_000\":\"OCCF\",\"reactant_002\":null,\"reactant_001\":\"NS(=O)(=O)c1ncccc1F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9940404295921326,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NS(=O)(=O)c1ncccc1OCCF\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][OH:4].[H-].[Na+].F[C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1>O1CCCC1>[F:1][CH2:2][CH2:3][O:4][C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1\",\"yield_000\":null}]","literatureScore":1,"label":"UA T5 AT LR TTL ALL>>166","id":166},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":768}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":768}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.71,"id":460,"pathId":768}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.34,"id":43,"pathId":768}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ZYHSNOOGZFKYJT","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":166,"pathId":768}],"RXN":"[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])F)[n:3][cH:2][n:1][c:13]2[Cl:14].[CH2:15]1[CH2:16][O:17][CH2:18][CH2:19][N:20]1[CH2:21][CH2:22][CH2:23][OH:24]>>[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])[O:24][CH2:23][CH2:22][CH2:21][N:20]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[n:3][cH:2][n:1][c:13]2[Cl:14];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.024,"id":19,"pathId":768}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":768}],"RXN":"[cH:27]1[cH:26][c:24]([c:31]([cH:30][c:28]1[NH2:29])[Cl:32])[F:25].[cH:11]1[c:10]2[c:5]([cH:4][c:3]([c:12]1[N+:13](=[O:15])[O-:14])[O:2][CH2:1][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[n:6][cH:7][n:8][c:9]2Cl>>[cH:27]1[cH:26][c:24]([c:31]([cH:30][c:28]1[NH:29][c:9]2[c:10]3[cH:11][c:12]([c:3]([cH:4][c:5]3[n:6][cH:7][n:8]2)[O:2][CH2:1][CH2:16][CH2:17][N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[N+:13](=[O:15])[O-:14])[Cl:32])[F:25];1.3.7;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":768}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":768}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":768}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":768}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.228","depth":0,"reaction":{"label":">>0","id":0,"pathId":1506},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":4,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0029944181442260742,\"rxn_id\":\"ord-e0b0f01cfc8846efa4465e6a5288872d\",\"index\":23488,\"rxn_smiles\":\"CC(C)OC(=O)N=NC(=O)OC(C)C.COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinazolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide (1.5 g, 2.96 mmol), 4-(3-hydroxypropyl)morpholine (0.623 mL, 4.5 mmol), triphenylphosphine (1.18 g, 4.5 mmol), and dichloromethane (50 mL) was added diisopropyl azodicarboxylate (0.886 mL, 4.5 mmol). The mixture was stirred at room temperature for 16 h, monitored by LCMS. After removal of solvent, the crude mixture was separated by flash column chromatography (silica), eluting with 5% methanol in dichloromethane to give N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N\\u2032-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (890 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.36 (br s, 1H), 10.05 (br s, 1H), 8.55 (s, 1H), 7.83 (m, 1H), 7.64 (m, 2H), 7.57 (s, 1H), 7.44 (m, 3H), 7.18 (t, 2H), 4.27 (m, 2H), 3.99 (s, 3H), 3.61 (m, 6H), 2.40 (m, 4H), 2.01 (m, 2H), 1.47 (m, 4H). LC\\/MS Calcd for [M+H]+ 634.2, found 634.3.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1O\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9970055818557739,\"agent_000\":\"CC(C)OC(=O)N=NC(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:37][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:36][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1\",\"yield_000\":47.5},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CCOCC\",\"distance\":0.003035128116607666,\"rxn_id\":\"ord-fab5133cf99a4d628c51ef65011713b7\",\"index\":182883,\"rxn_smiles\":\"CCCCP(CCCC)CCCC.CCOCC.COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O.ClCCl.O=C(N=NC(=O)N1CCCCC1)N1CCCCC1.OCCN1CCSCC1>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"procedure_details\":\"4-(2-Hydroxyethyl)thiomorpholine (114 mg, 0.78 mmol), (J. Am. Chem. Soc. 1934. 56, 1720), in methylene chloride (1 ml) followed by 1,1\\u2032-(azodicarbonyl)dipiperidine (525 mg. 2.08 mmol) were added to a stirred solution of 4-(4-chloro-2-fluoroanilino)7-hydroxy-6 methoxyquinazoline (225 mg, 0.70 mmol), (prepared as described for the starting material in Example 2), and tributylphosphine (0.51 ml, 2.08 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours and allowed to stand for a further 18 hours. Ether (8 ml) was added, the precipitate removed by filtration and the solvent removed from the filtrate by evaporation. The residue was dissolved in acetone and ethereal hydrogen chloride (2.5 m! of a 1M solution) added. The precipitated product was collected by filtration and purified by column chromatography eluting with methylene chloride\\/methanol\\/aqueous ammonia (150\\/8\\/1). The purified product was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazoline (70 mg, 22%) as a pale yellow solid.\",\"reactant_000\":\"OCCN1CCSCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O\",\"rxn_time\":3.5,\"reactant_003\":null,\"similarity\":0.9969648718833923,\"agent_000\":\"CCCCP(CCCC)CCCC\",\"agent_001\":\"O=C(N=NC(=O)N1CCCCC1)N1CCCCC1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCN1CCSCC1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][S:7][CH2:6][CH2:5]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40](O)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[Cl:28][C:29]1[CH:48]=[CH:47][C:32]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([O:1][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][S:7][CH2:6][CH2:5]4)=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)=[C:31]([F:49])[CH:30]=1\",\"yield_000\":22.3},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0032836198806762695,\"rxn_id\":\"ord-14091c5c560c40b28422ab56234f92cf\",\"index\":168156,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.CN(C)C=O.COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was added a solution of diethyl azodicarboxylate (101 μl; 0.64 mmol) in methylene chloride (0.4 ml). The mixture was stirred for 12 hours at 4° C. and overnight at ambient temperature. The mixture was poured onto a column of silica (IST isolute® 10 g of silica) and was eluted with methylene chloride (15 ml) followed by 5% methanol in methylene chloride (45 ml) followed by 5% methanol (saturated with ammonia) in methylene chloride (30 ml) followed by 10% methanol (saturated with ammonia) in methylene chloride (45 ml) followed by 15% methanol (saturated with ammonia) in methylene chloride (30 ml). The fractions containing the expected product were evaporated to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-morpholinopropoxy)quinazoline (63 mg, 44%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9967163801193237,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":4.0,\"product_000\":\"COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].O[CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:9]=[CH:8][N:7]=[C:6]2[NH:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2\",\"yield_000\":44.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0037235617637634277,\"rxn_id\":\"ord-ae2e2a15cfb44e3c8c0bddafaf4489b5\",\"index\":501292,\"rxn_smiles\":\"C1CCOC1.CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C.Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O.OCCc1ccncc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"procedure_details\":\"To a solution of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea (0.1 g, 0.24 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and triphenylphosphine (0.0944 g, 0.36 mmol) in 10 mL of dry THF was added diisopropylazo-dicarboxylate (0.0728 g, 0.36 mmol) at ambient temperature. The mixture was stirred for 2 hours. Next, additional triphenylphosphine (0.0944 g, 0.36 mmol), 4-(2-hydroxyethyl)-pyridine (0.0443 g, 0.36 mmol), and diisopropylazodicarboxylate were added and the reaction mixture further stirred at room temperature overnight. The solvent from the reaction mixture was evaporated and the crude residue was dissolved in 5.0 mL of DMSO and purified by RP-HPLC. The proper fractions were collected and concentrated to ¼ volume. The aqueous solution was neutralized with 1N NaOH and extracted with ethyl acetate (2×, 59 mL). The organic layer was dried with sodium sulfate, filtered and evaporated to dryness to afford 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyridin-4-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea as a brown solid in 44% yield. LCMS m\\/z (%)=526 (M+H 79Br, 100), 528 (M+H 81Br, 67). 1H NMR (DMSO-d6) δ: 9.33 (bs, 1H), 9.24 (bs, 1H), 8.39 (dd, J=4.44 and 1.48 Hz, 2H), 7.63 (d, J=7.28 Hz, 1H), 7.59 (s, 1H), 7.56 (dd, J=8.94 and 2.71 Hz, 2H), 7.48 (m, 1H), 7.34 (d, J=2.67, 1H), 7.31 (d, J=2.67, 1H), 7.28 (dd, J=6.88 and 4.87 Hz, 2H), 7.14 (d, J=9.05 Hz, 1H), 7.09 (d, J=5.93 Hz, 1H), 4.01-4.2 (m, 2H), 3.48 (s, 3H), 2.96-2.91 (m, 2H).\",\"reactant_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCc1ccncc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9962764382362366,\"agent_000\":\"CC(C)OC(=O)\\/N=N\\/C(=O)OC(C)C\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCc1ccncc1\",\"rxn_str\":\"[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[OH:14].O[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(\\/N=N\\/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[O:17])[CH:11]=[CH:12][C:13]=1[O:14][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1\",\"yield_000\":44.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.0038225650787353516,\"rxn_id\":\"ord-33bfcf35bf734b52b59d70aa5d195f4f\",\"index\":462262,\"rxn_smiles\":\"CCOC(=O)N=NC(=O)OCC.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.ClCCl.OCCCN1CCOCC1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Diethyl azodicarboxylate (2.67 ml, 17 mmol) was added dropwise to a solution of 3-morpholinopropan-1-ol (1.54 g, 10 mmol), 7-hydroxy-3,4-dihydro-6-methoxy-3-((pivaloyloxy)methyl)quinazolin-4-one (2.6 g, 8.5 mmol) and triphenylphosphine (4.45 g, 17 mmol) in methylene chloride (40 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride\\/methanol (97\\/3 followed by 95\\/5) to give 3,4-dihydro-6-methoxy-3-((pivaloyloxy)metyl)-7-(3-morpholinopropoxy)quinazolin-4-one (3.6 g, 97%).\",\"reactant_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961774349212646,\"agent_000\":\"CCOC(=O)N=NC(=O)OCC\",\"agent_001\":\"c1ccc(P(c2ccccc2)c2ccccc2)cc1\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]1.O[C:24]1[CH:33]=[C:32]2[C:27]([C:28](=[O:42])[N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[N:31]2)=[CH:26][C:25]=1[O:43][CH3:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:44][O:43][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:24]=1[O:22][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[N:31]=[CH:30][N:29]([CH2:34][O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]2=[O:42]\",\"yield_000\":97.7}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1506}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1506}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":1506}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":1506}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.42,"id":154,"pathId":1506}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":1506}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":1506}],"RXN":"[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[OH:17])[N+:19](=[O:21])[O-:20])[Cl:3])[F:5].[CH2:25]1[CH2:26][O:27][CH2:28][CH2:29][N:24]1[CH2:30][CH2:31][CH2:32]O>C(C)CCP(CCCC)CCCC.ClCCl.C1CN(CCC1)C(N=NC(N2CCCCC2)=O)=O>[cH:7]1[cH:6][c:4]([c:2]([cH:1][c:8]1[NH:9][c:10]2[c:23]3[cH:22][c:18]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:32][CH2:31][CH2:30][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[N+:19](=[O:21])[O-:20])[Cl:3])[F:5];1.7.7;Mitsunobu"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1506}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1506}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1506}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1506}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1506}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.251","depth":0,"reaction":{"label":">>0","id":0,"pathId":292},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.003749549388885498,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962504506111145,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"CC(C)(C)O\",\"distance\":0.00415647029876709,\"rxn_id\":\"ord-5510c71cc19244ccb4d87f14f34e8de5\",\"index\":424079,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"procedure_details\":\"To a solution of 4-chloro-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine (40 mg, 0.15 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 1 ml) was added 3-chloro-4-fluoroaniline (22 mg, 0.15 mmol). The mixture was heated at 90° C. for 2 days. After cooling down to room temperature, the solvents were removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 100:1) to yield the title compound as a white solid (28 mg, 50%).\",\"reactant_000\":\"Fc1ccc(-c2cc3c(Cl)ncnc3s2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9958435297012329,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3s2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[CH:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":49.9},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.004578828811645508,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9954211711883545,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004691362380981445,\"rxn_id\":\"ord-1706282351e44a6a96c8cda1fd077e00\",\"index\":312255,\"rxn_smiles\":\"CN(C)C=O.COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Nc1c(F)cc(Cl)cc1F.[H-].[Na+]>>COc1cc2c(Nc3c(F)cc(Cl)cc3F)ncnc2cc1OCC1CCN(C)CC1\",\"procedure_details\":\"Using an analogous procedure to that described in Example 4, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (246 mg, 0.764 mmol), (prepared as described for the starting material in Example 2c), was reacted with 4-chloro-2,6-difluoroaniline (250 mg, 1.53 mmol), (see WO 97\\/30035 Example 15), in DMF (9 ml) and in the presence of sodium hydride (60%, 76.5 mg, 1.9 mmol) to give 4-(4-chloro-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (210 mg, 61%).\",\"reactant_000\":\"Nc1c(F)cc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9953086376190186,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3c(F)cc(Cl)cc3F)ncnc2cc1OCC1CCN(C)CC1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH2:28])=[C:26]([F:32])[CH:25]=1.[H-].[Na+]>CN(C=O)C>[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH:28][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[C:26]([F:32])[CH:25]=1\",\"yield_000\":61.2},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.005193650722503662,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9948063492774963,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004627108573913574,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9953728914260864,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.005324959754943848,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9946750402450562,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0059626102447509766,\"rxn_id\":\"ord-46b7aabe19fa4743a938b1aaa2a0a56d\",\"index\":662518,\"rxn_smiles\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3F)n2)c1.OCCCF>>CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCCCF)n2)c1\",\"procedure_details\":\"Starting with 4-(2,4-difluorophenyl)-N-{3-[(methylsulfonyl)methyl]phenyl}-1,3,5-triazin-2-amine (75 mg; 0.197 mmol), intermediate 42.1, and 3-fluoropropan-1-ol (59 mg; 0.736 mmol), example 54 was prepared analogously to the procedure for the preparation of example 42.\",\"reactant_000\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3F)n2)c1\",\"reactant_002\":null,\"reactant_001\":\"OCCCF\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994037389755249,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCCCF)n2)c1\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:17]=2)[N:10]=1.[F:27][CH2:28][CH2:29][CH2:30][OH:31]>>[F:8][C:6]1[CH:5]=[CH:4][C:3]([C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:17]=3)[N:10]=2)=[C:2]([O:31][CH2:30][CH2:29][CH2:28][F:27])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006279468536376953,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.993720531463623,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006436705589294434,\"rxn_id\":\"ord-855ef139e6ed4c179e58d194cc378f0b\",\"index\":33547,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.O[C@@H]1CCOC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@@H]1CCOC1\",\"procedure_details\":\"13.80 g of potassium tert-butoxide are added batchwise to a solution of 10.80 g of (R)-3-hydroxytetrahydrofuran in 100 ml of N,N-dimethylformamide while cooling with an ice bath. The reaction mixture is stirred for about one hour, then 10.40 g of 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-fluoroquinazoline are added batchwise. The cooling bath is then removed and the deep red reaction mixture is stirred for two hours at ambient temperature. For working up the reaction mixture is poured onto about 500 ml of water and neutralized with 2 N hydrochloric acid. The yellowish precipitate formed is suction filtered and dried at 70° C. in a circulating air drier. Yield: 12.80 g; melting point: 244° C.; mass spectrum (ESI−): m\\/z=403, 405 [M−H]−.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O[C@@H]1CCOC1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9935632944107056,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@@H]1CCOC1\",\"rxn_str\":\"CC(C)([O-])C.[K+].[OH:7][C@@H:8]1[CH2:12][CH2:11][O:10][CH2:9]1.[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20].Cl>CN(C)C=O.O>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:7][C@@H:8]4[CH2:12][CH2:11][O:10][CH2:9]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA ER ALL>>495","id":495},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":292}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":292}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.098,"id":460,"pathId":292}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.33,"id":92,"pathId":292}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOWKNWPFXSSYBZ","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2Cl","intrinsicScore":0.26,"id":495,"pathId":292}],"RXN":"[cH:5]1[c:6]2[c:12]([cH:13][c:14]([c:4]1[N+:2](=[O:1])[O-:3])F)[n:11][cH:10][n:9][c:7]2[Cl:8].[CH2:17]([CH2:16][OH:15])[CH2:18][Cl:19]>>[cH:5]1[c:6]2[c:12]([cH:13][c:14]([c:4]1[N+:2](=[O:1])[O-:3])[O:15][CH2:16][CH2:17][CH2:18][Cl:19])[n:11][cH:10][n:9][c:7]2[Cl:8];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.26,"id":19,"pathId":292}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":292}],"RXN":"[cH:22]1[cH:23][c:24]([c:19]([cH:20][c:21]1[NH2:26])[Cl:27])[F:25].[cH:4]1[c:3]2[c:2]([cH:12][c:6]([c:5]1[N+:13](=[O:14])[O-:15])[O:7][CH2:8][CH2:9][CH2:10][Cl:11])[n:1][cH:18][n:17][c:16]2Cl>>[cH:22]1[cH:23][c:24]([c:19]([cH:20][c:21]1[NH:26][c:16]2[c:3]3[cH:4][c:5]([c:6]([cH:12][c:2]3[n:1][cH:18][n:17]2)[O:7][CH2:8][CH2:9][CH2:10][Cl:11])[N+:13](=[O:14])[O-:15])[Cl:27])[F:25];1.3.7;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":292}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":292}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":292}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":292}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":292}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.314","depth":0,"reaction":{"label":">>0","id":0,"pathId":1068},"children":[{"depth":1,"reaction":{"scalabilityModelScore":9,"literature":"[{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.01821732521057129,\"rxn_id\":\"ord-16ae0445dfd94e7da2080bdc98744209\",\"index\":285954,\"rxn_smiles\":\"C1COCCN1.CC#N.Cc1nc(NC(=O)CCCl)sc1-c1ccnc(Nc2ccc(Cl)cc2)n1>>Cc1nc(NC(=O)CCN2CCOCC2)sc1-c1ccnc(Nc2ccc(Cl)cc2)n1\",\"procedure_details\":\"By treatment of 3-chloro-N-{5-[2-(4-chloro-phenylamino)-pyrimidin-4-yl]-4-methyl-thiazol-2-yl}-propionamide with morpholine. Anal. RP-HPLC: tR=12.7 min (10-70% MeCN, purity >95%). 1H-NMR (CDCl3) δ: 1.50 (m, 2H, CH2), 2.52 (s, 3H, CH3), 3.05-3.78 (m, 8H, CH2), 3.81 (m, 2H, CH2), 7.12 (d, 1H, J=5.5 Hz, pyrimidinyl-H), 7.30 (d, 2H, J=7.0 Hz, Ph-H), 7.80 (d, 2H, J=7.0 Hz, Ph-H), 8.51 (d, 1H, J=5.0 Hz, pyrimidinyl-H), 9.80 (brs, 1H, NH).\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nc(NC(=O)CCCl)sc1-c1ccnc(Nc2ccc(Cl)cc2)n1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9817826747894287,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nc(NC(=O)CCN2CCOCC2)sc1-c1ccnc(Nc2ccc(Cl)cc2)n1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[S:8][C:9]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:14]=2)=[C:10]([CH3:12])[N:11]=1)=[O:5].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>CC#N>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:15]2[N:14]=[C:13]([C:9]3[S:8][C:7]([NH:6][C:4](=[O:5])[CH2:3][CH2:2][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[N:11][C:10]=3[CH3:12])[CH:18]=[CH:17][N:16]=2)=[CH:21][CH:22]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018659234046936035,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.981340765953064,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.019160926342010498,\"rxn_id\":\"ord-75ec29a1399f4ce6998dc52c12adc171\",\"index\":22085,\"rxn_smiles\":\"C1COCCN1.CN1CC(CCCl)N(C)c2nc3ccccc3n2C1=O>>CN1CC(CCN2CCOCC2)N(C)c2nc3ccccc3n2C1=O\",\"procedure_details\":\"To 3.0 g (0.0103 mol) of 2-(2-chloroethyl)-3,4-dihydro-1,4-dimethyl-1H-[1,3,5]triazepino[3,2-a]benzimidazol-5(2H)-one was added 20 mL of morpholine. The mixture was stirred at 60° C. for 4 hr. The morpholine was removed at 60° C. and approximately 1 mm Hg. The residue was partitioned between 100 mL of CH2Cl2 and 100 mL of 1N NaOH. The basic layer was reextracted with 50 mL of CH2Cl2. The combined organic extracts were dried over Na2SO4, filtered, and concentrated by rotary evaporation. The residue was crystallized from isopropyl alcohol to afford 2.1 g (59%) of white analytically pure crystals, mp 149°-151.5° C.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"CN1CC(CCCl)N(C)c2nc3ccccc3n2C1=O\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9808390736579895,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":60.0,\"product_000\":\"CN1CC(CCN2CCOCC2)N(C)c2nc3ccccc3n2C1=O\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH:4]1[N:17]([CH3:18])[C:9]2=[N:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:8]2[C:7](=[O:19])[N:6]([CH3:20])[CH2:5]1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1>>[CH3:18][N:17]1[C:9]2=[N:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:8]2[C:7](=[O:19])[N:6]([CH3:20])[CH2:5][CH:4]1[CH2:3][CH2:2][N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.020302534103393555,\"rxn_id\":\"ord-942141859e6a4f699148c474582ac24d\",\"index\":71800,\"rxn_smiles\":\"C1CNCCNC1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCCCCCl>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCCCCN1CCCNCC1\",\"procedure_details\":\"The title compound was prepared from 8-(6-chlorohexyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one (Intermediate 4) and 1,4-diazepane following the procedure outlined in Example 18, Step 2 (modifications: 40° C., 8 h). 1H NMR (400 MHz, DMSO-d6): δ 8.68 (s, 2H), 7.85 (d, 1H), 7.00 (d, 1H), 4.69 (s, 1H), 3.95 (t, 2H), 3.88 (s, 3H), 2.79 (t, 2H), 2.74 (m, 2H), 2.60-2.52 (m, 4H), 2.40 (t, 2H), 1.74 (m, 2H), 1.63 (m, 2H), 1.39 (m, 4H), 1.30 (m, 2H) [NH's not seen]; MS (ESI): 534.3.\",\"reactant_000\":\"C1CNCCNC1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9796974658966064,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCCCCN1CCCNCC1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[C:10]([O:29][CH3:30])=[CH:11][CH:12]=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[C:14]2[NH:20][C:21]1[C:26]([Cl:27])=[CH:25][N:24]=[CH:23][C:22]=1[Cl:28].[NH:31]1[CH2:37][CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>>[N:31]1([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]2[C:10]([O:29][CH3:30])=[CH:11][CH:12]=[C:13]3[C:18]=2[NH:17][C:16](=[O:19])[CH:15]=[C:14]3[NH:20][C:21]2[C:22]([Cl:28])=[CH:23][N:24]=[CH:25][C:26]=2[Cl:27])[CH2:37][CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.021074771881103516,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9789252281188965,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null}]","literatureScore":0.98,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003733396530151367,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962666034698486,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0045563578605651855,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9954436421394348,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.005399823188781738,\"rxn_id\":\"ord-c8665eba631f41fd986e3dd0e0027af3\",\"index\":232057,\"rxn_smiles\":\"CCN(CC)CC.ClCCl.Nc1cc(C(F)(F)F)ccc1Br.O=C(Cl)CCl>>O=C(CCl)Nc1cc(C(F)(F)F)ccc1Br\",\"procedure_details\":\"To a solution of 2-bromo-5-trifluoromethylaniline (10.0 g) in methylene chloride (100 ml) was added triethylamine and the solution was cooled to 0° C. To this solution was slowly added choroacetyl chloride and the reaction mixture was allowed to cool to room temperature overnight. The solution was concentrated and the resulting solid was extracted with ethyl acetate. The organic extract was first washed with 10% HCl (2×2 ml), then with water (12×25 ml) and was collected, dried and evaporated to obtain the title compound (yield, 10.2 g). 1HNMR (250 MHz, CDCl3): 4.22 (s, 2 H), 7.26 (d, J=8 Hz, 1 H), 7.66 (d, J=8 Hz, 1 Hz), 8.68 (s, 1 H), 9.02 (br s, 1 H).\",\"reactant_000\":\"Nc1cc(C(F)(F)F)ccc1Br\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9946001768112183,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(CCl)Nc1cc(C(F)(F)F)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:3]=1[NH2:4].C(N(CC)CC)C.[Cl:20][CH2:21][C:22](Cl)=[O:23]>C(Cl)Cl>[Br:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:10])([F:11])[F:12])=[CH:5][C:3]=1[NH:4][C:22](=[O:23])[CH2:21][Cl:20]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005453646183013916,\"rxn_id\":\"ord-d1541f1fc9724eb2b742dac21120d55b\",\"index\":498839,\"rxn_smiles\":\"ClC(Cl)Cl.Nc1ccc(C(=O)c2ccccc2)cc1.O=C(Cl)CCCl.[Na+].[OH-]>>O=C(CCCl)Nc1ccc(C(=O)c2ccccc2)cc1\",\"procedure_details\":\"A solution of 3.95 g of p-aminobenzophenone in 100 ml of chloroform was treated with 2.6 g of 3-chloropropionyl chloride and, after the addition of 26 ml of 1N sodium hydroxide solution, stirred at room temperature. The organic phase was separated, washed in sequence with water, 1N HCl and water, dried and evaporated. After recrystallization from methanol of the oil obtained there was obtained 4-(3-chloropropionamido)benzophenone, m.p. 135°-136° C.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)c2ccccc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945463538169861,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)c2ccccc2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[Cl:16][CH2:17][CH2:18][C:19](Cl)=[O:20].[OH-].[Na+]>C(Cl)(Cl)Cl>[Cl:16][CH2:17][CH2:18][C:19]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:15])=[CH:6][CH:7]=1)=[O:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.005779743194580078,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9942202568054199,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4}]","literatureScore":1,"label":"LR ER AT UA ALL>>76","id":76},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1068}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1068}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1068}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.024,"id":34,"pathId":1068}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.77,"id":70,"pathId":1068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UMODJRMAPGXEHQ","smiles":"FC1=CC=C(NC2=C3C=C(NC(=O)CCCl)C(OCCCCl)=CC3=NC=N2)C=C1Cl","intrinsicScore":0.19,"id":76,"pathId":1068}],"RXN":"[cH:25]1[cH:26][c:27]([c:29]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][Cl:23])[NH2:24])[Cl:30])[F:28].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:25]1[cH:26][c:27]([c:29]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][Cl:23])[NH:24][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:30])[F:28];2.1.1;Amide"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.024,"id":9,"pathId":1068}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1068}],"RXN":"[cH:4]1[cH:5][c:6]([c:1]([cH:2][c:3]1[NH:8][c:9]2[c:10]3[cH:18][c:17]([c:16]([cH:15][c:11]3[n:12][cH:13][n:14]2)[O:25][CH2:26][CH2:27][CH2:28]Cl)[NH:19][C:20](=[O:24])[CH2:21][CH2:22][Cl:23])[Cl:29])[F:7].[CH2:32]1[CH2:31][O:30][CH2:35][CH2:34][NH:33]1>>[cH:4]1[cH:5][c:6]([c:1]([cH:2][c:3]1[NH:8][c:9]2[c:10]3[cH:18][c:17]([c:16]([cH:15][c:11]3[n:12][cH:13][n:14]2)[O:25][CH2:26][CH2:27][CH2:28][N:33]4[CH2:32][CH2:31][O:30][CH2:35][CH2:34]4)[NH:19][C:20](=[O:24])[CH2:21][CH2:22][Cl:23])[Cl:29])[F:7];1.6.4;Chloro"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1068}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.378","depth":0,"reaction":{"label":">>0","id":0,"pathId":1825},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.04800713062286377,\"rxn_id\":\"ord-dff5feb3a030455a92fbd7d37a9a0070\",\"index\":302674,\"rxn_smiles\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1.COCCOC.[Na+].[OH-]>>CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"procedure_details\":\"To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v\\/v\\/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.\",\"reactant_000\":\"COCCOC\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(C2CCCN(C)C2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9519928693771362,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1\",\"rxn_str\":\"[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]\",\"yield_000\":65.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.050463080406188965,\"rxn_id\":\"ord-3e17ab538baa4ea69a93a016a295dfb3\",\"index\":479522,\"rxn_smiles\":\"CC(=O)OC(C)=O.Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O>>CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"procedure_details\":\"A solution of 9-amino-3,4-dihydroacridin-1(2H)-one N-oxide (5.4 g) and acetic anhydride (60 ml) was heated to reflux and then concentrated. The residue was stirred in saturated sodium bicarbonate solution for one hr. The mixture was filtered and the filter cake was washed with water and dried under vacuum at 40° C. for three hrs to yield 1.93 g of product, mp 208° C. (dec). An additional 1.38 g, mp 208° C. (dec), of product was obtained by extraction of the tiltrate with ethyl acetate, evaporation of ethyl acetate extract, and trituration of the residue with diethyl ether; total 52% yield.\",\"reactant_000\":\"CC(=O)OC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1c2c([n+]([O-])c3ccccc13)CCCC2=O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.949536919593811,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)OC1CCC(=O)c2c1nc1ccccc1c2N\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]2[C:8]([N+:9]([O-])=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([O:21][CH:11]1[C:10]2[C:15](=[C:2]([NH2:1])[C:3]3[C:8]([N:9]=2)=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:14](=[O:16])[CH2:13][CH2:12]1)(=[O:20])[CH3:19]\",\"yield_000\":52.0},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.05079483985900879,\"rxn_id\":\"ord-022206f9de2642b2bd1eb74d065e111e\",\"index\":440086,\"rxn_smiles\":\"CCOC(C)=O.CO.COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1.[Pd]>>COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"procedure_details\":\"To a solution of [2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-(2-methoxy-ethyl)-methyl-amine (0.8 g, 2.1 mmol) in 4:1 ethyl acetate\\/methanol (50 ml) under nitrogen, was added 5% palladium on carbon (100 mg) and the mixture was first evacuated and then stirred at room temperature under an atmosphere of hydrogen for 1 day. The reaction mixture was then filtered through Celite, washed with 1:1 ethyl acetate\\/methanol (10 mL) and the combined filtrate and washings were concentrated to give the crude 4-{5-[2-(2-methoxy-ethoxy)-ethylamino]-1H-benzoimidazol-2-yl}-benzene-1,2-diamine as a thick oil that was used in the next step without any purification.\",\"reactant_000\":\"CCOC(C)=O\",\"reactant_002\":null,\"reactant_001\":\"COCCN(C)c1ccc2[nH]c(-c3ccc(N)c([N+](=O)[O-])c3)nc2c1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9492051601409912,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COCCOCCNc1ccc2[nH]c(-c3ccc(N)c(N)c3)nc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([N:17]([CH2:19][CH2:20][O:21][CH3:22])C)=[CH:16][C:10]=3[N:9]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.[C:26]([O:29][CH2:30]C)(=O)C.CO>[Pd]>[CH3:26][O:29][CH2:30][CH2:22][O:21][CH2:20][CH2:19][NH:17][C:15]1[CH:14]=[CH:13][C:11]2[NH:12][C:8]([C:5]3[CH:4]=[C:3]([NH2:23])[C:2]([NH2:1])=[CH:7][CH:6]=3)=[N:9][C:10]=2[CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.054064929485321045,\"rxn_id\":\"ord-868c3e11c46245968f1bc57f73633de2\",\"index\":102173,\"rxn_smiles\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2.CC(=O)OC(C)=O.O>>C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"procedure_details\":\"To 4.8 g of 4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline-N-oxide was added 50 ml of acetic anhydride, and the mixture was stirred at 90° C. for 5 hours. After the reaction was completed, acetic anhydride was removed by evaporation under reduced pressure, to the residue thus obtained was added water and then extracted with chloroform. The chloroform layer was washed with an aqueous solution of sodium hydroxide and an aqueous solution saturated with sodium chloride, then dried with anhydrous magnesium sulfate. Chloroform was removed by evaporation under reduced pressure to obtain 5.0 g of 8-acetoxy-4-allyloxy-3-methyl-5,6,7,8-tetrahydroquinoline in the form of brown oily substance.\",\"reactant_000\":\"C=CCOc1c(C)c[n+]([O-])c2c1CCCC2\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)OC(C)=O\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.945935070514679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"C=CCOc1c(C)cnc2c1CCCC2OC(C)=O\",\"rxn_str\":\"[CH2:1]([O:4][C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N+:8]([O-])=[CH:7][C:6]=1[CH3:16])[CH:2]=[CH2:3].[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>O>[C:17]([O:20][CH:10]1[C:9]2[N:8]=[CH:7][C:6]([CH3:16])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[C:14]=2[CH2:13][CH2:12][CH2:11]1)(=[O:19])[CH3:18]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.0547868013381958,\"rxn_id\":\"ord-88d328a4c09344b7bc1b6396f39a2e59\",\"index\":367880,\"rxn_smiles\":\"CO.Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1.[Pd]>>CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"procedure_details\":\"1-Methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide (150 mg, 0.371 mmol; see step (ii) above) was suspended in methanol (25 mL) to which Pd\\/C-10% (108 mg) was added at 0° C. under a nitrogen with stirring. The reaction mixture was hydrogenated for 5 h at room temperature and atmospheric pressure. The catalyst was removed over Kieselguhr and methanol was removed under reduced pressure to give the title compound, which was used without further purification.\",\"reactant_000\":\"Cn1cc(NC(=O)c2cc([N+](=O)[O-])cn2C)cc1C(=O)NCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9452131986618042,\"agent_000\":\"[Pd]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CN(C)CCCNC(=O)c1cc(NC(=O)c2cc(N)cn2C)cn1C\",\"rxn_str\":\"[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([NH:21][CH2:22][CH2:23]N1CCOCC1)=[O:20]>CO.[Pd]>[NH2:15][C:13]1[CH:14]=[C:10]([C:8]([NH:7][C:5]2[CH:4]=[C:3]([C:19]([NH:21][CH2:22][CH2:23][CH2:1][N:2]([CH3:6])[CH3:3])=[O:20])[N:2]([CH3:1])[CH:6]=2)=[O:9])[N:11]([CH3:18])[CH:12]=1\",\"yield_000\":null}]","literatureScore":0.95,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.011562705039978027,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.988437294960022,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.012491464614868164,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9875085353851318,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.012716531753540039,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.98728346824646,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.014612674713134766,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9853873252868652,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015181660652160645,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9848183393478394,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"ER AT UA TTL ALL>>37","id":37},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002956986427307129,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9970430135726929,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.003121674060821533,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968783259391785,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.004679560661315918,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9953204393386841,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.00482785701751709,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9951721429824829,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005971133708953857,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9940288662910461,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"AT ER UA ALL>>171","id":171},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":7,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":8,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1825}]},{"depth":8,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1825}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":1825}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":7,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":1825}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.62,"id":487,"pathId":1825}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":6,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.051,"id":43,"pathId":1825}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"SHBNRYHTAYAZRE","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":171,"pathId":1825}],"RXN":"[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])F)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>C1CCCO1.[Na]>[cH:10]1[cH:11][c:12]([c:13]([cH:15][c:9]1[NH:8][c:3]2[c:2]3[cH:17][c:18]([c:19]([cH:20][c:1]3[n+:6]([cH:5][n:4]2)[O-:7])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:21](=[O:23])[O-:22])[Cl:14])[F:16];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OLQIBSLYLBDMMQ","smiles":"NC1=C(OCCC[NH+]2CCOCC2)C=C2C(=C1)C(NC1=CC(Cl)=C(F)C=C1)=NC=[N+]2[O-]","intrinsicScore":0.1,"id":37,"pathId":1825}],"RXN":"[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:25])[F:29]>>[cH:28]1[cH:27][c:26]([c:24]([cH:23][c:22]1[NH:21][c:20]2[c:14]3[cH:13][c:12]([c:11]([cH:16][c:15]3[n+:17]([cH:18][n:19]2)[O-:30])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:25])[F:29];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1825}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCC[NH+]4CCOCC4)N)Cl)F>C(C)(=O)O.CO.ClC(Cl)Cl.[Fe]>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)N)Cl)F;0.0;Unrecognized"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1825}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1825}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1825}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1825}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.384","depth":0,"reaction":{"label":">>0","id":0,"pathId":2},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.7,"literature":"[{\"solvent_000\":\"CCOCC\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.022724628448486328,\"rxn_id\":\"ord-2c2d9dc39d0d474a85061a120a39d396\",\"index\":743514,\"rxn_smiles\":\"C1COCCO1.CC(=O)[O-].CC(=O)[O-].CCOCC.COc1ccc(N)cc1.O=[N+]([O-])c1ccc(Br)cc1.[Pd+2].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>>COc1ccc(Nc2ccc([N+](=O)[O-])cc2)cc1\",\"procedure_details\":\"A mixture of palladium acetate (37 mg, 0.165 mmol) and BINAP (154 mg, 0.248 mmol) in 5 mL dioxane was stirred for 10 min under Ar atmosphere. To this mixture was added 1-bromo-4-nitrobenzene (1.11 g, 5.5 mmol), 4-methoxyaniline (745 mg, 6.07 mmol), CsCO3 (2.5 g, 7.73 mmol), and 10 mL of dioxane. The mixture was heated at reflux for 15 h and cooled and diluted with ether (80 mL). The solid was removed through filtration and the filtrate was concentrated. The residue was chromatographed (hexane\\/EtOAc) to afford 4-methoxy-N-(4-nitrophenyl)aniline as a yellow solid (786 mg, 58%). MS (ESI) m\\/z 245 (M+H+).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(Br)cc1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc(N)cc1\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.9772753715515137,\"agent_000\":\"[Pd+2]\",\"agent_001\":\"CC(=O)[O-]\",\"agent_002\":\"c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1\",\"temperature\":null,\"product_000\":\"COc1ccc(Nc2ccc([N+](=O)[O-])cc2)cc1\",\"rxn_str\":\"Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1>O1CCOCC1.CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)=[CH:15][CH:14]=1\",\"yield_000\":58.5},{\"solvent_000\":\"Cc1ccccc1C\",\"solvent_001\":null,\"distance\":0.0254974365234375,\"rxn_id\":\"ord-29344fb506244a22afe413519460364c\",\"index\":185086,\"rxn_smiles\":\"CC(C)(C)OC(=O)N1CCC(N)CC1.CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1.Cc1ccccc1C.Fc1ccc(Br)cc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.[Pd].[Pd]>>CC(C)(C)OC(=O)N1CCC(Nc2ccc(F)cc2)CC1\",\"procedure_details\":\"Under a nitrogen atmosphere, a xylene solution (65 mL) of tert-butyl 4-amino-piperidine-1-carboxylate (1.00 g, 5.00 mmol), 4-bromo-1-fluorobenzene (0.500 mL, 4.57 mmol), 2\\u2032-(dicyclohexylphosphino)-N,N-dimethyl-[1,1\\u2032-biphenyl]-2-amine (360 mg, 1.00 mmol), and tris(dibenzylideneacetone)dipalladium (0) (209 mg, 0.250 mmol) was stirred at 140° C. for 4 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography (hexane\\/ethyl acetate=100\\/0→70\\/30 (v\\/v)) to obtain the title compound (980 mg, yield 66%).\",\"reactant_000\":\"Fc1ccc(Br)cc1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OC(=O)N1CCC(N)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9745025634765625,\"agent_000\":\"[Pd]\",\"agent_001\":\"CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1\",\"agent_002\":\"O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1\",\"temperature\":null,\"product_000\":\"CC(C)(C)OC(=O)N1CCC(Nc2ccc(F)cc2)CC1\",\"rxn_str\":\"[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.Br[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C(C)=CC=CC=1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([NH:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)=[CH:17][CH:18]=1\",\"yield_000\":72.8},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.025520920753479004,\"rxn_id\":\"ord-3d2a849917d6437193f10944d561968b\",\"index\":484714,\"rxn_smiles\":\"C[Si](C)(C)c1ccc(Br)cc1.Cc1ccccc1.Nc1cc(F)c(-c2ccccc2)cc1F.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.[Na].[Pd].[Pd]>>C[Si](C)(C)c1ccc(Nc2cc(F)c(-c3ccccc3)cc2F)cc1\",\"procedure_details\":\"4-phenyl-2,5-difluoroaniline (12 mmol), 4-bromo-trimethylsilylbenzene (10 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.15 mmol), (±)-2,2\\u2032-bis(diphenylphosphine)-1,1\\u2032-binaphthalene (0.3 mmol) and sodium tert-butoxie (14 mmol) are put in a two-neck round-bottom flask and dissolved in toluene (30 mL). Subsequently, the resulting solution is stirred in a bath under a temperature of about 100° C. for 24 hours. After completion of the reaction, toluene is removed. The reaction mixture is extracted with dichloromethane and water, and then being distilled under reduced pressure. The resulting residence is filtered by silica gel column and distilled under reduced pressure again. Next, by re-crystallizing and filtering with dichloromethane and petroleum ether, 4-phenyl-2,5-difluoro-N-(4-trimethylsilylphenyl)benzenamine (2.6 g) is yielded.\",\"reactant_000\":\"Nc1cc(F)c(-c2ccccc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)c1ccc(Br)cc1\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.974479079246521,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"C[Si](C)(C)c1ccc(Nc2cc(F)c(-c3ccccc3)cc2F)cc1\",\"rxn_str\":\"[C:1]1([C:7]2[C:13]([F:14])=[CH:12][C:10]([NH2:11])=[C:9]([F:15])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:17]1[CH:22]=[CH:21][C:20]([Si:23]([CH3:26])([CH3:25])[CH3:24])=[CH:19][CH:18]=1.[Na]>C1(C)C=CC=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]1([C:7]2[C:13]([F:14])=[CH:12][C:10]([NH:11][C:17]3[CH:22]=[CH:21][C:20]([Si:23]([CH3:26])([CH3:25])[CH3:24])=[CH:19][CH:18]=3)=[C:9]([F:15])[CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1\",\"yield_000\":73.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.02568131685256958,\"rxn_id\":\"ord-6cd110eee6174f3aa18857980214df92\",\"index\":372639,\"rxn_smiles\":\"CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1.COc1ncc(Br)cc1CCCN(C)C.Nc1ncc2c(n1)-c1ccc(Cl)cc1NC(=O)C2.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.[Pd].[Pd]>>COc1ncc(Nc2ncc3c(n2)-c2ccc(Cl)cc2NC(=O)C3)cc1CCCN(C)C\",\"procedure_details\":\"A mixture of 2-amino-9-chloro-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one (0.36 g, 1.38 mmol), 3-(5-bromo-2-methoxypyridin-3-yl)-N,N-dimethylpropan-1-amine (0.38 g, 1.38 mmol), xphos (0.047 g, 0.099 mmol), and tris(dibenzylideneacetone)dipalladium(0) (0.023 g, 0.026 mmol) in a sealed microwave tube was evacuated and purged with nitrogen three times. To the solids were added tert-butyl alcohol (3.6 mL) and t-BuOK (1M in t-BuOH, 2.63 mL) via syringe. The mixture was stirred well and then subjected to microwave irradiation (150 watts) while heating at 150° C. for 45 min. The reaction mixture was then poured into water (25 mL) with vigorous stirring. The precipitate that formed was filtered, washed with water, and air dried. The residue was purified by column chromatography to give 9-chloro-2-({5-[3-(dimethylamino)propyl]-6-methoxypyridin-3-yl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one (0.125 g, 18%).\",\"reactant_000\":\"Nc1ncc2c(n1)-c1ccc(Cl)cc1NC(=O)C2\",\"reactant_002\":null,\"reactant_001\":\"COc1ncc(Br)cc1CCCN(C)C\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9743186831474304,\"agent_000\":\"[Pd]\",\"agent_001\":\"CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1\",\"agent_002\":\"O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1\",\"temperature\":150.0,\"product_000\":\"COc1ncc(Nc2ncc3c(n2)-c2ccc(Cl)cc2NC(=O)C3)cc1CCCN(C)C\",\"rxn_str\":\"[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:6][C:7](=[O:18])[NH:8][C:9]3[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:10]=3[C:11]=2[N:12]=1.Br[C:20]1[CH:21]=[C:22]([CH2:28][CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])[C:23]([O:26][CH3:27])=[N:24][CH:25]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:17][C:15]1[CH:14]=[CH:13][C:10]2[C:11]3[N:12]=[C:2]([NH:1][C:20]4[CH:25]=[N:24][C:23]([O:26][CH3:27])=[C:22]([CH2:28][CH2:29][CH2:30][N:31]([CH3:32])[CH3:33])[CH:21]=4)[N:3]=[CH:4][C:5]=3[CH2:6][C:7](=[O:18])[NH:8][C:9]=2[CH:16]=1\",\"yield_000\":20.0},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.026021718978881836,\"rxn_id\":\"ord-bc715d726b214670b8b515c9efd95368\",\"index\":134011,\"rxn_smiles\":\"Cc1ccccc1.Fc1ccccc1Br.Nc1ccc(-c2ccccc2)cc1-c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1.[Na].[Pd].[Pd]>>Fc1ccccc1Nc1ccc(-c2ccccc2)cc1-c1ccccc1\",\"procedure_details\":\"2,4-diphenylaniline (12 mmol), 1-bromo-2-fluorobenzene (10 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.15 mmol), (±)-2,2\\u2032-bis(diphenylphosphine)-1,1\\u2032-binaphthalene (0.3 mmol) and sodium tert-butoxie (14 mmol) are put in a two-neck round-bottom flask and dissolved in toluene (30 mL). Subsequently, the resulting solution is stirred in a bath under a temperature of about 100° C. for 24 hours. After completion of the reaction, toluene is removed. The reaction mixture is extracted with dichloromethane and water, and then being distilled under reduced pressure. The resulting residence is filtered by silica gel column and distilled under reduced pressure again. Next, by re-crystallizing and filtering with dichloromethane and petroleum ether, 2,4-diphenyl-N-2-fluorophenylbenzenamine (2.1 g) is yielded.\",\"reactant_000\":\"Nc1ccc(-c2ccccc2)cc1-c1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccccc1Br\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9739782810211182,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C(\\/C=C\\/c1ccccc1)\\/C=C\\/c1ccccc1\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"Fc1ccccc1Nc1ccc(-c2ccccc2)cc1-c1ccccc1\",\"rxn_str\":\"[C:1]1([C:7]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:10][C:8]=2[NH2:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[F:27].[Na]>C1(C)C=CC=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.C1C=CC(\\/C=C\\/C(\\/C=C\\/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]1([C:7]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:10][C:8]=2[NH:9][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[F:27])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1\",\"yield_000\":61.9}]","literatureScore":0.98,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004261016845703125,\"rxn_id\":\"ord-c852f738cd874053b847da34a32d27f9\",\"index\":340005,\"rxn_smiles\":\"CC(C)O.O=[N+]([O-])c1ccc(Br)cc1Nc1ccnc(Cl)n1.[NH4+].[OH-]>>Nc1nccc(Nc2cc(Br)ccc2[N+](=O)[O-])n1\",\"procedure_details\":\"To a solution of N-(5-bromo-2-nitrophenyl)-2-chloropyrimidin-4-amine (6 g, 18.21 mmol) in 2-propanol (70 mL), in a pressure vessel, was carefully added ammonium hydroxide solution (150 mL) at RT. The reaction vessel was sealed and stirred at 90° C. (at 4.5 bar pressure) for 20 hr. The reaction mixture was cooled to 0° C. The resulting precipitate was collected by vacuum filtration, washed with water and dried in the vacuum oven to afford the title compound as an orange solid: 1H NMR (250 MHz, DMSO) δ 6.17 (1H, d, J=5.63 Hz), 6.34 (2H, br. s.), 7.39 (1H, dd, J=8.83, 1.98 Hz), 7.89-7.99 (2H, m), 8.34 (1H, d, J=2.13 Hz), 9.62 (1H, s); LC-MS: m\\/z+309.9, 311.7 (M+H)+.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(Br)cc1Nc1ccnc(Cl)n1\",\"reactant_002\":null,\"reactant_001\":\"[NH4+]\",\"rxn_time\":20.0,\"reactant_003\":null,\"similarity\":0.9957389831542969,\"agent_000\":\"[OH-]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Nc1nccc(Nc2cc(Br)ccc2[N+](=O)[O-])n1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N+:16]([O-:18])=[O:17])=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11](Cl)[N:10]=2)[CH:7]=1.[OH-].[NH4+:20]>CC(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N+:16]([O-:18])=[O:17])=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH2:20])[N:10]=2)[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.004271984100341797,\"rxn_id\":\"ord-1bcd3184a8ff4d60b219145e85c3fa70\",\"index\":664484,\"rxn_smiles\":\"CO.N.O=[N+]([O-])c1ccc2c(Cl)ncnc2c1>>Nc1ncnc2cc([N+](=O)[O-])ccc12\",\"procedure_details\":\"A mixture of 1.6 g of 4-chloro-7-nitroquinazoline in 50 ml 7N ammonia in methanol was stirred overnight at rt and concentrated to dryness. The solid was suspended in water, filtered, rinsed with water followed by ether and dried overnight in vacuum oven to provide 0.98 g of 7-nitroquinazolin-4-amine (compound 98-2).\",\"reactant_000\":\"O=[N+]([O-])c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"N\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9957280158996582,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ncnc2cc([N+](=O)[O-])ccc12\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([N+:12]([O-:14])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH3:15]>CO>[N+:12]([C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH2:15])=[N:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1)([O-:14])=[O:13]\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004658639430999756,\"rxn_id\":\"ord-5d1097f9520a4e3d90b819b8a3daa6db\",\"index\":479340,\"rxn_smiles\":\"CC(C)O.O=[N+]([O-])c1cc(F)c(Br)cc1Nc1ccnc(Cl)n1.[NH4+].[NH4+].[OH-]>>Nc1nccc(Nc2cc(Br)c(F)cc2[N+](=O)[O-])n1\",\"procedure_details\":\"To a solution of N-(5-bromo-4-fluoro-2-nitrophenyl)-2-chloropyrimidin-4-amine (1.05 g, 3.02 mmol) in 2-propanol (12 mL) in a pressure vessel was added ammonium hydroxide (12 mL, 303 mmol) carefully at RT. The reaction vessel was sealed and stirred at 90° C. for 15 hr (4 bar). Extra aqueous ammonium (4 mL, 100 mmol) was added and the reaction heated at 90° C. for 1 hr then cooled to 0° C. The resultant orange precipitate was filtered and dried by suction filtration to afford the title compound as an orange solid (713 mg, 63% yield); 1H NMR (500 MHz, DMSO) delta 9.55 (s, 1H), 8.44 (d, J=6.6 Hz, 1H), 8.17 (d, J=8.6 Hz, 1H), 7.98 (d, J=5.6 Hz, 1H), 6.31 (s, 2H), 6.19 (d, J=5.6 Hz, 1H); LC-MS: m\\/z+329.80 (M+H)+.\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1Nc1ccnc(Cl)n1\",\"reactant_002\":null,\"reactant_001\":\"[NH4+]\",\"rxn_time\":15.0,\"reactant_003\":null,\"similarity\":0.9953413605690002,\"agent_000\":\"[OH-]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Nc1nccc(Nc2cc(Br)c(F)cc2[N+](=O)[O-])n1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([F:19])=[CH:4][C:5]([N+:16]([O-:18])=[O:17])=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11](Cl)[N:10]=2)[CH:7]=1.[OH-].[NH4+:21].[NH4+]>CC(O)C>[Br:1][C:2]1[C:3]([F:19])=[CH:4][C:5]([N+:16]([O-:18])=[O:17])=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH2:21])[N:10]=2)[CH:7]=1\",\"yield_000\":72.0},{\"solvent_000\":\"O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.005372166633605957,\"rxn_id\":\"ord-87d465a7c8a146dbb6734610ebfc96e2\",\"index\":132671,\"rxn_smiles\":\"C1COCCO1.N.O.O=[N+]([O-])c1cccc(-n2cc(I)c3c(Cl)ncnc32)c1>>Nc1ncnc2c1c(I)cn2-c1cccc([N+](=O)[O-])c1\",\"procedure_details\":\"A solution of 4-chloro-5-iodo-7-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine (500 mg, 1.25 mmol), NH3.H2O (3 mL) and dioxane (6 mL) in a sealed tube was heated to 120° C. in a microwave reactor for 40 min. The yellow precipitate was collected by filtration to provide 5-iodo-7-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (69) (460 mg, 97%). LC-MS (ESI): m\\/z (M+1) 382.\",\"reactant_000\":\"O=[N+]([O-])c1cccc(-n2cc(I)c3c(Cl)ncnc32)c1\",\"reactant_002\":null,\"reactant_001\":\"N\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994627833366394,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ncnc2c1c(I)cn2-c1cccc([N+](=O)[O-])c1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH3:21].O>O1CCOCC1>[I:11][C:10]1[C:3]2[C:2]([NH2:21])=[N:7][CH:6]=[N:5][C:4]=2[N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[CH:9]=1\",\"yield_000\":97.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005769193172454834,\"rxn_id\":\"ord-b3d0836a4c97405c8a028095057366da\",\"index\":400140,\"rxn_smiles\":\"ClCc1ccc2c(Cl)ncnc2c1.N>>Nc1ncnc2cc(CCl)ccc12\",\"procedure_details\":\"To 15 ml of a saturated ethanolic ammonia solution is added 1.0 g (4.7 mmole) of 4-chloro-7-chloromethylquinazoline. The mixture is stirred at room temperature overnight. The precipitate which forms is collected to give 0.7 g of the title intermediate product, mp>300° C.; 77% yield. 1H NMR (d6-DMSO, 300 MHz) δ 8.38 (s, 1H), 8.20 (d, 1H), 7.78 (bs, 2H), 7.70 (s, 1H), 7.51 (d, 1H), 4.92 (s, 2H). EI MS, [M]+=193, 195 (Cl pattern).\",\"reactant_000\":\"ClCc1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"N\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9942308068275452,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ncnc2cc(CCl)ccc12\",\"rxn_str\":\"[NH3:1].Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([CH2:13][Cl:14])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1>>[NH2:1][C:3]1[C:12]2[C:7](=[CH:8][C:9]([CH2:13][Cl:14])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1\",\"yield_000\":77.0}]","literatureScore":1,"label":"TTL ALL>>168","id":168},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0024016499519348145,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9975983500480652,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0034421682357788086,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9965578317642212,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005340635776519775,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9946593642234802,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005926012992858887,\"rxn_id\":\"ord-61db4d46573641b09a365452241e4a72\",\"index\":23563,\"rxn_smiles\":\"C1CCOC1.CCc1nc2cc(F)ccc2[n+]([O-])n1.O.OCCCN1CCOCC1.[H-].[Na+]>>CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"procedure_details\":\"NaH (60% dispersion in oil, 310 mg, 7.75 mmol) was added to dry THF (10 mL) and stirred at 20° C. for 20 min prior to the addition of 3-(4-morpholinyl)propanol (676 mg, 4.66 mmol). The mixture was stirred for 30 min, fluoride 28 (300 mg, 1.55 mmol) added and the resulting solution stirred at 20° C. for 2.5 h under N2. Water was added and the solution extracted with DCM (4×30 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by column chromatography, eluting with a gradient (0-5%) MeOH\\/DCM to give 1-oxide 31 (257 mg, 52%) as a pale yellow solid, mp 108-111° C.; 1H NMR δ 8.33 (d, J=9.3 Hz, 1 H, H-8), 7.21-7.26 (m, 2 H, H-7 and H-5), 4.22 (t, J=6.4 Hz, 2 H, CH2), 3.73 (t, J=4.6 Hz, 4 H, 2×CH2O), 3.00 (q, J=7.6 Hz, 2 H, CH2), 2.55 (t, J=7.0 Hz, 2 H, CH2), 2.48 (t, J=4.6 Hz, 4 H, 2×CH2N), 2.06 (m, 2 H, CH2), 1.43 (t, J=7.6 Hz, 3 H, CH3); 13C NMR δ 168.7, 164.6, 150.3, 128.4, 123.1, 121.6, 106.3, 67.3 (2), 66.9, 55.1, 53.7 (2), 30.7, 26.0, 12.2. Anal. Calcd for C16H22N4O3: C, 60.4; H, 7.0; N, 17.6. Found: C, 60.4; H, 7.0; N, 17.4%.\",\"reactant_000\":\"CCc1nc2cc(F)ccc2[n+]([O-])n1\",\"reactant_002\":null,\"reactant_001\":\"OCCCN1CCOCC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9940739870071411,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1\",\"rxn_str\":\"[H-].[Na+].C1COCC1.[N:8]1([CH2:14][CH2:15][CH2:16][OH:17])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27](F)=[CH:26][C:24]=2[N:25]=1)[CH3:19]>O>[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27]([O:17][CH2:16][CH2:15][CH2:14][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:26][C:24]=2[N:25]=1)[CH3:19]\",\"yield_000\":52.1},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005959570407867432,\"rxn_id\":\"ord-a73cb883fae1487ca599634bf5ed7e4b\",\"index\":602333,\"rxn_smiles\":\"C1CCOC1.NS(=O)(=O)c1ncccc1F.OCCF.[H-].[Na+]>>NS(=O)(=O)c1ncccc1OCCF\",\"procedure_details\":\"5.76 ml of 2-fluoroethanol are added dropwise, with cooling, to a suspension of 6.54 g of sodium hydride (55.6% NaH in oil) in 120 ml of tetrahydrofuran so that the temperature does not exceed 20° C. When the dropwise addition is complete, the reaction mixture is stirred at room temperature for 15 minutes and then a further solution of 10.56 g of 3-fluoro-pyrid-2-ylsulfonamide in 60 ml of tetrahydrofuran is added dropwise over a period of 10 minutes. The reaction solution is then stirred for 10 minutes at room temperature and for 2 hours at reflux before it is cooled and concentrated. For purification, the oil remaining is chromatographed on a silica gel column using ethyl acetate\\/hexane 4\\/1. Evaporation of the eluant yields a light-coloured oil which crystallises spontaneously, yielding 5.88 g of title product which melts at 122°-123° C.\",\"reactant_000\":\"OCCF\",\"reactant_002\":null,\"reactant_001\":\"NS(=O)(=O)c1ncccc1F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9940404295921326,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NS(=O)(=O)c1ncccc1OCCF\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][OH:4].[H-].[Na+].F[C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1>O1CCCC1>[F:1][CH2:2][CH2:3][O:4][C:8]1[C:9]([S:14]([NH2:17])(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1\",\"yield_000\":null}]","literatureScore":1,"label":"UA T5 AT LR TTL ALL>>166","id":166},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":6,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":2}]},{"depth":6,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":2}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.71,"id":460,"pathId":2}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.34,"id":43,"pathId":2}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ZYHSNOOGZFKYJT","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1OCCCN1CCOCC1","intrinsicScore":0.12,"id":166,"pathId":2}],"RXN":"[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])F)[n:3][cH:2][n:1][c:13]2[Cl:14].[CH2:15]1[CH2:16][O:17][CH2:18][CH2:19][N:20]1[CH2:21][CH2:22][CH2:23][OH:24]>>[cH:11]1[c:12]2[c:4]([cH:5][c:6]([c:7]1[N+:8](=[O:9])[O-:10])[O:24][CH2:23][CH2:22][CH2:21][N:20]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[n:3][cH:2][n:1][c:13]2[Cl:14];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"TTL ALL>>36","id":36},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"QGZKDVFQNNGYKY","smiles":"N","intrinsicScore":0.12,"id":36,"pathId":2}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OWNZPAZKNISHOX","smiles":"NC1=NC=NC2=C1C=C(C(OCCCN1CCOCC1)=C2)[N+]([O-])=O","intrinsicScore":0.024,"id":168,"pathId":2}],"RXN":"[cH:6]1[c:7]2[c:12]([cH:13][c:14]([c:5]1[N+:2](=[O:3])[O-:4])[O:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[n:11][cH:10][n:9][c:8]2Cl.[NH4+:1]>>[cH:6]1[c:7]2[c:12]([cH:13][c:14]([c:5]1[N+:2](=[O:3])[O-:4])[O:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[n:11][cH:10][n:9][c:8]2[NH2:1];9.7.39;Chloro"},{"depth":3,"reaction":{"label":"TTL ALL>>112","id":112},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"CJTIWGBQCVYTQE","smiles":"FC1=C(Cl)C=C(Br)C=C1","intrinsicScore":0.024,"id":112,"pathId":2}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":2}],"RXN":"[cH:2]1[cH:3][c:4]([c:5]([cH:7][c:1]1Br)[Cl:6])[F:8].[cH:28]1[c:22]2[c:21]([cH:20][c:19]([c:29]1[N+:30](=[O:32])[O-:31])[O:18][CH2:9][CH2:10][CH2:11][N:12]3[CH2:13][CH2:14][O:15][CH2:16][CH2:17]3)[n:27][cH:26][n:25][c:23]2[NH2:24]>C1COCCO1.O=C([O-])C.O1C2=C(P(C3=CC=CC=C3)C4=CC=CC=C4)C=CC=C2C(C5=CC=CC(=C15)P(C6=CC=CC=C6)C7=CC=CC=C7)(C)C.O=C([O-])[O-].[Cs+].[Pd+2]>[cH:2]1[cH:3][c:4]([c:5]([cH:7][c:1]1[NH:24][c:23]2[c:22]3[cH:28][c:29]([c:19]([cH:20][c:21]3[n:27][cH:26][n:25]2)[O:18][CH2:9][CH2:10][CH2:11][N:12]4[CH2:13][CH2:14][O:15][CH2:16][CH2:17]4)[N+:30](=[O:32])[O-:31])[Cl:6])[F:8];1.3.6;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":2}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":2}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.387","depth":0,"reaction":{"label":">>0","id":0,"pathId":1936},"children":[{"depth":1,"reaction":{"scalabilityModelScore":7.3,"literature":"[{\"solvent_000\":\"c1ccccc1\",\"solvent_001\":null,\"distance\":0.05510491132736206,\"rxn_id\":\"ord-1dc4c2dcbd484499bf4d0d95e7d51419\",\"index\":576501,\"rxn_smiles\":\"CC(C)(C)[O-].Cn1c(CCCl)cnc1[N+](=O)[O-].[K+].c1ccccc1>>C=Cc1cnc([N+](=O)[O-])n1C\",\"procedure_details\":\"To a solution of 18.9 g. of 5-(2-chloroethyl)-1-methyl-2-nitroimidazole (prepared according to the procedure of British Pat. No. 1,222,486) in 2.8 liters of anhydrous benzene cooled to 5°-10° C., 16.8 g. of potassium tert-butoxide is added. Stirring is continued for 2 hours at 5°-10° C. After filtration and concentration to dryness under vacuum at a temperature lower than 50° C., the resulting yellow oily residue is washed three times with 50 ml. of ethyl ether (or light petroleum). The title product is obtained, which is dried under vacuum at 40° C.; yield 12 g. (77.7%). A sample crystallized from ethyl ether melts at 106°-108° C.\",\"reactant_000\":\"Cn1c(CCCl)cnc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9448950886726379,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=Cc1cnc([N+](=O)[O-])n1C\",\"rxn_str\":\"Cl[CH2:2][CH2:3][C:4]1[N:8]([CH3:9])[C:7]([N+:10]([O-:12])=[O:11])=[N:6][CH:5]=1.CC(C)([O-])C.[K+]>C1C=CC=CC=1>[CH3:9][N:8]1[C:4]([CH:3]=[CH2:2])=[CH:5][N:6]=[C:7]1[N+:10]([O-:12])=[O:11]\",\"yield_000\":null},{\"solvent_000\":\"c1ccccc1\",\"solvent_001\":\"CS(C)=O\",\"distance\":0.05664736032485962,\"rxn_id\":\"ord-2681ffbcba474e329a835516b5fa7468\",\"index\":15652,\"rxn_smiles\":\"CC(C)(C)[O-].CC(C)C[C@H]1[C@H](CCCl)OC(C)(C)N1C(=O)OCc1ccccc1.CS(C)=O.[K+].c1ccccc1>>C=C[C@@H]1OC(C)(C)N(C(=O)OCc2ccccc2)[C@H]1CC(C)C\",\"procedure_details\":\"610 mg of (4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-5-(2-chloroethyl)-4-isobutyloxazolidine was dissolved in 3.6 ml of dry benzene, and a solution prepared by dissolving 390 mg of potassium tert-butoxide in 3.6 ml of dimethyl sulfoxide, was added thereto. The mixture was reacted at room temperature for 10 minutes. The reaction solution thus obtained was purified by silica gel column chromatography (packed with 36 g of silica gel, developer: benzene\\/ethyl acetate (30\\/1)), and the fraction containing the desired compound was collected and concentrated. The residue thus obtained was dried under reduced pressure to obtain 540 mg (yield: 99%) of (4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-5-ethenyl-4-isobutyloxazolidine as a colorless transparent syrup having the following physical properties.\",\"reactant_000\":\"CC(C)C[C@H]1[C@H](CCCl)OC(C)(C)N1C(=O)OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9433526396751404,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=C[C@@H]1OC(C)(C)N(C(=O)OCc2ccccc2)[C@H]1CC(C)C\",\"rxn_str\":\"[CH2:1]([O:8][C:9]([N:11]1[C@@H:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[C@H:14]([CH2:20][CH2:21]Cl)[O:13][C:12]1([CH3:24])[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+]>C1C=CC=CC=1.CS(C)=O>[CH2:1]([O:8][C:9]([N:11]1[C@@H:15]([CH2:16][CH:17]([CH3:18])[CH3:19])[C@H:14]([CH:20]=[CH2:21])[O:13][C:12]1([CH3:24])[CH3:23])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":98.7},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.05698651075363159,\"rxn_id\":\"ord-73d6a92a2a31482e87844c85a874153f\",\"index\":108343,\"rxn_smiles\":\"CC(C)=O.O=C(CCCl)OCC(O)(C(=O)c1ccccc1)c1ccccc1.O=C([O-])[O-].[K+].[K+]>>C=CC(=O)OCC(O)(C(=O)c1ccccc1)c1ccccc1\",\"procedure_details\":\"7.8 g (23.4 mmol) (2,3-diphenyl-2-hydroxy-3-oxopropyl)-3-chloro-propionate was dissolved in 75 ml acetone. 4.9 g (35.1 mmol) K2CO3 and 50 mg BHT were added and the mixture was refluxed for 5 hours. The inorganic salts were removed by filtration and the solvent was evaporated under reduced pressure. The residue was treated with 50 ml n.-hexane, 2,3-diphenyl-2-hydroxy-3-oxopropyl acrylate was isolated by filtration and dried. 6.3 g of 2,3-diphenyl-2-hydroxy-3-oxopropyl acrylate (91%) was isolated. Based on 1H-NMR-analysis the conversion proved to be 98%.\",\"reactant_000\":\"O=C(CCCl)OCC(O)(C(=O)c1ccccc1)c1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9430134892463684,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)OCC(O)(C(=O)c1ccccc1)c1ccccc1\",\"rxn_str\":\"[C:1]1([C:7]([OH:23])([C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:16])[CH2:8][O:9][C:10](=[O:14])[CH2:11][CH2:12]Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[C:10]([O:9][CH2:8][C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([OH:23])[C:15]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:16])(=[O:14])[CH:11]=[CH2:12]\",\"yield_000\":null},{\"solvent_000\":\"COCCOC\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.05837982892990112,\"rxn_id\":\"ord-5b2facec2b954355b536a232b0cc3482\",\"index\":295682,\"rxn_smiles\":\"CCN(CC)CC.COCCOC.Cn1nc(Cl)c(Cl)c1S(=O)(=O)CCCl>>C=CS(=O)(=O)c1c(Cl)c(Cl)nn1C\",\"procedure_details\":\"To a solution of 2.2 g (0.022 moles) triethylamine in 75 ml dimethoxyethane, 5 g (0.018 moles) 1-methyl-3,4-dichloro-5-(2-chloroethylsulfonyl)pyrazole were added. The reaction mixture was stirred at ambient temperature for about one hour and then heated to reflux and refluxed about 2 hours. The reaction mixture was filtered, and the filtrate was stripped to give a yellow oil. The oil was chromatographed on silica gel eluting with methylene chloride yielding a thick oil which crystallized upon cooling with dry ice. Recrystallization from methylene chloride-hexane gave the product as a white solid, melting point 66°-69° C.\",\"reactant_000\":\"Cn1nc(Cl)c(Cl)c1S(=O)(=O)CCCl\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9416201710700989,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CS(=O)(=O)c1c(Cl)c(Cl)nn1C\",\"rxn_str\":\"C(N(CC)CC)C.[CH3:8][N:9]1[C:13]([S:14]([CH2:17][CH2:18]Cl)(=[O:16])=[O:15])=[C:12]([Cl:20])[C:11]([Cl:21])=[N:10]1>C(COC)OC>[CH3:8][N:9]1[C:13]([S:14]([CH:17]=[CH2:18])(=[O:16])=[O:15])=[C:12]([Cl:20])[C:11]([Cl:21])=[N:10]1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.060659050941467285,\"rxn_id\":\"ord-7bb2b429758e42b9b2e0126b055008c1\",\"index\":199511,\"rxn_smiles\":\"CCN(CC)CC.Cc1ccccc1.O=C([O-])[O-].O=S(=O)(CCCl)c1ccccc1.[K+].[K+]>>C=CS(=O)(=O)c1ccccc1\",\"procedure_details\":\"(β-chloroethylsulfonyl)benzene (40.9 g, 200 mmol) was dissolved in 100 g of toluene, to this solution were added 30.7 g of 49% aqueous potassium carbonate solution (potassium carbonate 109 mmol) and 1.01 g (10 mmol) of triethylamine, and the mixture was stirred for 3 hours at from 40 to 45° C. Then, the mixture was washed with 70 g of water once, with 35 g of 5% aqueous sulfuric acid solution once and further with 35 g of water once, and the solvents were distilled off to obtain 33.1 g (yield 98.4%) of phenylvinylsulfone.\",\"reactant_000\":\"O=S(=O)(CCCl)c1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9393409490585327,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":42.5,\"product_000\":\"C=CS(=O)(=O)c1ccccc1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][S:4]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[O:6])=[O:5].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(N(CC)CC)C>[C:7]1([S:4]([CH:3]=[CH2:2])(=[O:6])=[O:5])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1\",\"yield_000\":98.4}]","literatureScore":0.94,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003733396530151367,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962666034698486,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0045563578605651855,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9954436421394348,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.005399823188781738,\"rxn_id\":\"ord-c8665eba631f41fd986e3dd0e0027af3\",\"index\":232057,\"rxn_smiles\":\"CCN(CC)CC.ClCCl.Nc1cc(C(F)(F)F)ccc1Br.O=C(Cl)CCl>>O=C(CCl)Nc1cc(C(F)(F)F)ccc1Br\",\"procedure_details\":\"To a solution of 2-bromo-5-trifluoromethylaniline (10.0 g) in methylene chloride (100 ml) was added triethylamine and the solution was cooled to 0° C. To this solution was slowly added choroacetyl chloride and the reaction mixture was allowed to cool to room temperature overnight. The solution was concentrated and the resulting solid was extracted with ethyl acetate. The organic extract was first washed with 10% HCl (2×2 ml), then with water (12×25 ml) and was collected, dried and evaporated to obtain the title compound (yield, 10.2 g). 1HNMR (250 MHz, CDCl3): 4.22 (s, 2 H), 7.26 (d, J=8 Hz, 1 H), 7.66 (d, J=8 Hz, 1 Hz), 8.68 (s, 1 H), 9.02 (br s, 1 H).\",\"reactant_000\":\"Nc1cc(C(F)(F)F)ccc1Br\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9946001768112183,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(CCl)Nc1cc(C(F)(F)F)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:3]=1[NH2:4].C(N(CC)CC)C.[Cl:20][CH2:21][C:22](Cl)=[O:23]>C(Cl)Cl>[Br:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:10])([F:11])[F:12])=[CH:5][C:3]=1[NH:4][C:22](=[O:23])[CH2:21][Cl:20]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005453646183013916,\"rxn_id\":\"ord-d1541f1fc9724eb2b742dac21120d55b\",\"index\":498839,\"rxn_smiles\":\"ClC(Cl)Cl.Nc1ccc(C(=O)c2ccccc2)cc1.O=C(Cl)CCCl.[Na+].[OH-]>>O=C(CCCl)Nc1ccc(C(=O)c2ccccc2)cc1\",\"procedure_details\":\"A solution of 3.95 g of p-aminobenzophenone in 100 ml of chloroform was treated with 2.6 g of 3-chloropropionyl chloride and, after the addition of 26 ml of 1N sodium hydroxide solution, stirred at room temperature. The organic phase was separated, washed in sequence with water, 1N HCl and water, dried and evaporated. After recrystallization from methanol of the oil obtained there was obtained 4-(3-chloropropionamido)benzophenone, m.p. 135°-136° C.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)c2ccccc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945463538169861,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)c2ccccc2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[Cl:16][CH2:17][CH2:18][C:19](Cl)=[O:20].[OH-].[Na+]>C(Cl)(Cl)Cl>[Cl:16][CH2:17][CH2:18][C:19]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:15])=[CH:6][CH:7]=1)=[O:20]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.005779743194580078,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9942202568054199,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4}]","literatureScore":1,"label":"LR ER AT UA ALL>>76","id":76},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1936}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1936}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1936}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1936}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1936}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.024,"id":34,"pathId":1936}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.77,"id":70,"pathId":1936}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UMODJRMAPGXEHQ","smiles":"FC1=CC=C(NC2=C3C=C(NC(=O)CCCl)C(OCCCCl)=CC3=NC=N2)C=C1Cl","intrinsicScore":0.024,"id":76,"pathId":1936}],"RXN":"[cH:25]1[cH:26][c:27]([c:29]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][Cl:23])[NH2:24])[Cl:30])[F:28].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:25]1[cH:26][c:27]([c:29]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][Cl:23])[NH:24][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:30])[F:28];2.1.1;Amide"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1936}],"RXN":"[cH:12]1[cH:13][c:14]([c:16]([cH:18][c:11]1[NH:10][c:9]2[c:8]3[cH:7][c:6]([c:24]([cH:23][c:22]3[n:21][cH:20][n:19]2)[O:25][CH2:26][CH2:27][CH2:28][Cl:29])[NH:5][C:2](=[O:1])[CH2:3][CH2:4]Cl)[Cl:17])[F:15]>>[CH2:4]=[CH:3][C:2](=[O:1])[NH:5][c:6]1[cH:7][c:8]2[c:22]([cH:23][c:24]1[O:25][CH2:26][CH2:27][CH2:28][Cl:29])[n:21][cH:20][n:19][c:9]2[NH:10][c:11]3[cH:12][cH:13][c:14]([c:16]([cH:18]3)[Cl:17])[F:15];9.7.254;Chloro"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1936}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1936}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-8.394","depth":0,"reaction":{"label":">>0","id":0,"pathId":1918},"children":[{"depth":1,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005597054958343506,\"rxn_id\":\"ord-ca4b13de141c4414b5fa8f07cc29c487\",\"index\":78436,\"rxn_smiles\":\"COc1cc(O)c(Br)cc1-c1ccc(F)cc1.ClCCCBr>>COc1cc(OCCCCl)c(Br)cc1-c1ccc(F)cc1\",\"procedure_details\":\"The title intermediate was prepared from 4-(2-methoxy-4-hydroxy-5-bromophenyl)fluorobenzene and 3-bromopropyl chloride in 84% yield by the procedure of Preparation 36. NMR\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(O)c(Br)cc1-c1ccc(F)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944029450416565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(OCCCCl)c(Br)cc1-c1ccc(F)cc1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:8]=[C:7]([OH:9])[C:6]([Br:10])=[CH:5][C:4]=1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1.Br[CH2:19][CH2:20][CH2:21][Cl:22]>>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:4]2[C:3]([O:2][CH3:1])=[CH:8][C:7]([O:9][CH2:19][CH2:20][CH2:21][Cl:22])=[C:6]([Br:10])[CH:5]=2)=[CH:12][CH:13]=1\",\"yield_000\":84.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.007161617279052734,\"rxn_id\":\"ord-7976216c70ed440c8975a4bb1bf4a648\",\"index\":330727,\"rxn_smiles\":\"CN(C)C=O.COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O.ClCCCBr.O.O=C([O-])[O-].[K+].[K+]>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCCCl\",\"procedure_details\":\"A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (957 mg, 3 mmol), (prepared as described for the starting material in Example 2), 1-bromo-3-chloropropane (2.36 g, 15 mmol) and potassium carbonate (2.1 g, 15 mmol) in DMF (20 ml) was heated at 40° C. for 1.5 hours. The mixture was allowed to cool, was diluted with water and extracted with ethyl acetate (3×50 ml). The organic extracts were combined, washed with water and brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with hexanelethyl acetate, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroaniiino)-7-(3-chloropropoxy)-6-methoxyquinazoline (650 mg, 55%).\",\"reactant_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9928383827209473,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCCCCl\",\"rxn_str\":\"[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Br[CH2:24][CH2:25][CH2:26][Cl:27].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:24][CH2:25][CH2:26][Cl:27])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1\",\"yield_000\":54.7},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.007268786430358887,\"rxn_id\":\"ord-2171d0b095f24fdcbe85c2efe7a9701a\",\"index\":785384,\"rxn_smiles\":\"CC(=O)Nc1cc(C(C)=O)ccc1O.CC(C)=O.ClCCCBr>>CC(=O)Nc1cc(C(C)=O)ccc1OCCCCl\",\"procedure_details\":\"A stirred mixture of 1-[3-acetylamino-4-hydroxyphenyl]ethanone (7.7 g, 40 mmol), K2CO2 (5.7 g), 3-chloro-1-bromopropane (8.9 g, 56 mmol) and acetone (100 ml) was refluxed for 16 hours. The reaction was allowed to cool to ambient temperature and filtered. Concentration of the filtrate yielded 8.5 g of a white solid. The solid was recrystallized from toluene and then from ethanol to afford 6.5 g of an off-white solid. A 3.3 g sample of this material was flash chromatographed on silica gel with ethyl acetate as eluent. Concentration of the appropriate fractions afforded 2.8 g of a solid. The solid was recrystallized from toluene and then from ethanol-water to yield 2.2 g (51%) of a solid, m.p.=124°-126° C.\",\"reactant_000\":\"CC(=O)Nc1cc(C(C)=O)ccc1O\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9927312135696411,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CC(=O)Nc1cc(C(C)=O)ccc1OCCCCl\",\"rxn_str\":\"[C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:12](=[O:14])[CH3:13])[CH:8]=[CH:9][C:10]=1[OH:11])(=[O:3])[CH3:2].[Cl:15][CH2:16][CH2:17][CH2:18]Br>CC(C)=O>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:12](=[O:14])[CH3:13])[CH:8]=[CH:9][C:10]=1[O:11][CH2:18][CH2:17][CH2:16][Cl:15])(=[O:3])[CH3:2]\",\"yield_000\":78.8},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0073738694190979,\"rxn_id\":\"ord-fe9b6d92a37a4f9b9fc2d2dea27ec3e2\",\"index\":100536,\"rxn_smiles\":\"CN(C)C=O.COc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1O.ClCCCBr.O.O=C([O-])[O-].[K+].[K+]>>COc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1OCCCCl\",\"procedure_details\":\"A mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (1.2 g, 3.3 mmol), (prepared as described for the starting material in Example 48), 1-bromo-3-chloropropane (1.6 ml, 16 mmol) and potassium carbonate (2.1 g, 15 mmol) in DMF (25 ml) was heated at 45° C. for 3 hours. The mixture was allowed to cool, was diluted with water and extracted with ethyl acetate (3×70 ml). The organic extracts were combined, washed with water and brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with hexantlethyl acetate, collected by filtration and dried under vacuum to give 4-(4-bromo-2-fluoroanihno)-7-(3-chloropropoxy)-6-methoxyquinazoline (492 mg, 34%).\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9926261305809021,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":45.0,\"product_000\":\"COc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1OCCCCl\",\"rxn_str\":\"[Br:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Br[CH2:24][CH2:25][CH2:26][Cl:27].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:24][CH2:25][CH2:26][Cl:27])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1\",\"yield_000\":33.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0076174139976501465,\"rxn_id\":\"ord-58be3460da164ecd837954de54b733b8\",\"index\":411792,\"rxn_smiles\":\"CC(=O)c1cccc(O)c1.ClCCCBr>>CC(=O)c1cccc(OCCCCl)c1\",\"procedure_details\":\"Prepared by Procedure U and Scheme AK using 1-(3-hydroxyphenyl)ethanone and 1-bromo-3-chloropropane.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)c1cccc(O)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9923825860023499,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)c1cccc(OCCCCl)c1\",\"rxn_str\":\"[OH:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.Br[CH2:12][CH2:13][CH2:14][Cl:15]>>[Cl:15][CH2:14][CH2:13][CH2:12][O:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0016717910766601562,\"rxn_id\":\"ord-7f4e5cc36887435cbbdc295e9f320425\",\"index\":760420,\"rxn_smiles\":\"C=CC(=O)O.Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1>>C=CC(=O)Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"procedure_details\":\"In a procedure analogous to Example 15, reaction of N1-(4-(pyridin-2-ylthio)pyrimidin-2-yl)benzene-1,3-diamine (35 mg, 0.12 mmol) and acrylic acid (16 μL, 0.24 mmol) furnished the product (18 mg, 43%).\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9983282089233398,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2nccc(Sc3ccccn3)n2)c1\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=2)[N:9]=1.[C:22](O)(=[O:25])[CH:23]=[CH2:24]>>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:16]=[C:17]([NH:21][C:22](=[O:25])[CH:23]=[CH2:24])[CH:18]=[CH:19][CH:20]=2)[N:9]=1\",\"yield_000\":42.9},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0018631219863891602,\"rxn_id\":\"ord-8b1771262c5e44ada19659657c7eb43e\",\"index\":412829,\"rxn_smiles\":\"C=CC(=O)O.Nc1cccc(Sc2ccnc(Cl)n2)c1>>C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"procedure_details\":\"In a procedure analogous to Example 15, reaction of 3-(2-chloropyrimidin-4-ylthio)benzenamine (300 mg, 1.26 mmol) and acrylic acid (173 μL, 2.52 mmol) furnished the product (250 mg, 68%).\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981368780136108,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1\",\"rxn_str\":\"[Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH2:15])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:16](O)(=[O:19])[CH:17]=[CH2:18]>>[Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1\",\"yield_000\":68.0},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004402875900268555,\"rxn_id\":\"ord-4094429492154f2dbcefff644399bdf5\",\"index\":480696,\"rxn_smiles\":\"C=CC(=O)O.CCN=C=NCCCN(C)C.CN(C)C=O.Cl.Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"procedure_details\":\"To a solution of 6-amino-4-[(3-bromophenyl)amino]-quinazoline (2.0 g, 6.35 mmol) in dry DMF (20 mL) under N2 was added acrylic acid (12.7 mmol, 0.87 mL). The resulting solution was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl) (7.62 mmol, 1.46 g) was added. The reaction was stirred at 0° C. for 15 minutes and then allowed to warm to room temperature and stirred for a further 2 hours, after which additional acrylic acid (0.30 mL) and EDCI·HCL (0.30 g) were added. After a further 2 hours, the reaction was complete by tlc, solvent was removed under reduced pressure, and the resulting residue diluted with saturated NaHCO3 and repeatedly extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Column chromatography on grade III alumina eluting with EtOAc\\/MeOH (95:5) followed by recrystallization from EtOAc\\/hexane gave a spongy white solid, which upon several hours under high vacuum gave N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.06 g, 45%) as a cream powder, mp 258-261° C.\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9955971240997314,\"agent_000\":\"CCN=C=NCCCN(C)C\",\"agent_001\":\"Cl\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1.[C:20](O)(=[O:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:20](=[O:23])[CH:21]=[CH2:22])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:18]=[CH:17][CH:16]=1\",\"yield_000\":45.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004851937294006348,\"rxn_id\":\"ord-f02e414320974bea8fe4ad495ef6df84\",\"index\":288038,\"rxn_smiles\":\"C\\/C=C\\/C(=O)O.Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1>>C\\/C=C\\/C(=O)Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1\",\"procedure_details\":\"(E)-N-(3-(4-(4-phenoxyphenoxy)pyridin-3-yl)phenyl)but-2-enamide was prepared from 3-(4-(4-phenoxyphenoxy)pyridin-3-yl)aniline and (E)-but-2-enoic acid using Method E (56% yield). HPLC: 98%, RT=4.292 min. MS: m\\/z=423 [M+H]+, RT=4.28 min. 1H-NMR (DMSO-d6) δ 9.91 (s, 1H), 8.52 (s, 1H), 8.43 (d, 1H), 7.92 (s, 1H), 7.68 (d, 1H), 7.40-7.37 (m, 3H), 7.30 (d, 1H), 7.18-7.12 (m, 3H), 7.08 (d, 2H), 7.02 (d, 2H), 6.83-6.76 (m, 2H), 6.14 (d, 1H), 1.86 (d, 3H).\",\"reactant_000\":\"C\\/C=C\\/C(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951480627059937,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C\\/C=C\\/C(=O)Nc1cccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)c1\",\"rxn_str\":\"[O:1]([C:8]1[CH:27]=[CH:26][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=2)[NH2:22])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28](O)(=[O:32])\\/[CH:29]=[CH:30]\\/[CH3:31]>>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:20]=[C:21]([NH:22][C:28](=[O:32])\\/[CH:29]=[CH:30]\\/[CH3:31])[CH:23]=[CH:24][CH:25]=2)=[CH:26][CH:27]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":56.0},{\"solvent_000\":\"CO\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.004852771759033203,\"rxn_id\":\"ord-bf24e611fd8c4b079f2ff4859f73f6ab\",\"index\":267419,\"rxn_smiles\":\"C=CC(=O)O.CCN=C=NCCCN(C)C.CN(C)C=O.CO.Cl.Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1>>C=CC(=O)Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"procedure_details\":\"To an ice-cold solution of 0.158 g (0.5 mM) of 7-amino-4-(3-bromoanilino)-quinazoline [J Med Chem, 1995:3482] and 0.108 g of acrylic acid in 5.0 mL of dry dimethylformamide (DMF) was added 0.288 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (EDAC). After stirring for 5 minutes, the mixture became a solution, and the ice bath was removed. The reaction continued to stir at room temperature for 3 hours. The reaction was then poured into a mixture of ice and water and made basic with the addition of a saturated solution of sodium bicarbonate. This aqueous mixture was extracted three times with ethyl acetate, and the pooled extracts were dried over magnesium sulfate. The solution was filtered and concentrated in vacuo to afford a light yellow solid. The solid was dissolved in 100 mL of methanol, filtered, and concentrated in vacuo to approximately 10 mL. The solid which precipitated from solution was collected and dried in vacuo at 80° C. to give 50 mg of N-[4-(3-bromo-phenylamino)-quinazolin-7-yl]acrylamide, mp >265° C. Chemical ionization mass spectra: m\\/e 369.\",\"reactant_000\":\"C=CC(=O)O\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9951472282409668,\"agent_000\":\"CCN=C=NCCCN(C)C\",\"agent_001\":\"Cl\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc2c(Nc3cccc(Br)c3)ncnc2c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:20](O)(=[O:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CO>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:6]2[C:5]3[C:10](=[CH:11][C:2]([NH:1][C:20](=[O:23])[CH:21]=[CH2:22])=[CH:3][CH:4]=3)[N:9]=[CH:8][N:7]=2)[CH:18]=[CH:17][CH:16]=1\",\"yield_000\":27.0}]","literatureScore":1,"label":"T5 AT UA TTL ER ALL>>12","id":12},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002769649028778076,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9972303509712219,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0031270384788513184,\"rxn_id\":\"ord-dcc1a5efa86d4d09b08ec14f86ec1748\",\"index\":264188,\"rxn_smiles\":\"Cl.O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12>>Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"procedure_details\":\"A solution of stannous chloride dihydrate (3.7 g, 16 mmol) in 10 ml of conc. hydrochloric acid was added dropwise to a stirred suspension of 2,3-dihydroxy-6-nitrobenzo(f)quinoxaline (1.3 g, 5 mmol) in 8 ml of conc. hydrochloric acid. Then the mixture was stirred at 60-70° C. on an oil bath for 2 h. After cooling on ice, the precipitate was collected, dissolved in boiling water (1 1), filtered while hot, and neutralized to pH 6 with solid sodium hydrogen carbonate. The yellow product was isolated and recrystallized from DMF\\/water, washed with water, ethanol and ether and finally dried at 110 ° C. to give 0.90 g (63%) of pure title compound, m.p. >300° C., IR (KBr): 1690, ? 1640 and 1605 cm-1,1H-NMR (DMSO-d6): 5.8 (broad s, 2H,NH2), 6.63(s,1H, H-5), 7.2-8.7 (m, 4H, ArH), 11.8 (broad s, 2H, 20H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968729615211487,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([OH:19])=[N:4][C:5]2[CH:6]=[C:7]([N+:16]([O-])=O)[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[N:11]=1>Cl>[NH2:16][C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]2[N:11]=[C:2]([OH:1])[C:3]([OH:19])=[N:4][C:5]=2[CH:6]=1\",\"yield_000\":79.2},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.00328141450881958,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9967185854911804,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003656148910522461,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963438510894775,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003899812698364258,\"rxn_id\":\"ord-fc93af0f0d9a40e284c2500298acaf93\",\"index\":573049,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"The crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine was dissolved in THF and reduced using Raney nickel catalyst to yield N4-(3-Chloro-4-fluoro-phenyl)-7-(2,2-difluoro-ethoxy)-quinazoline-4,6-diamine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961001873016357,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C1COCC1.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null}]","literatureScore":1,"label":"UA CF T5 AT ER TTL ALL>>33","id":33},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1918}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":1918}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":1918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.68,"id":154,"pathId":1918}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEFNIUDZICAGOU","smiles":"NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1O","intrinsicScore":0.65,"id":33,"pathId":1918}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[N+:21](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[NH2:21])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.65,"id":6,"pathId":1918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ZZFBJRRZEBIWHH","smiles":"OC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1NC(=O)C=C","intrinsicScore":0.21,"id":12,"pathId":1918}],"RXN":"[CH2:4]=[CH:3][C:2](=[O:1])O.[cH:11]1[cH:12][c:5]([c:7]([cH:9][c:10]1[NH:13][c:14]2[c:15]3[cH:20][c:19]([c:18]([cH:17][c:16]3[n:23][cH:24][n:25]2)[OH:22])[NH2:21])[Cl:8])[F:6]>>[CH2:4]=[CH:3][C:2](=[O:1])[NH:21][c:19]1[cH:20][c:15]2[c:16]([cH:17][c:18]1[OH:22])[n:23][cH:24][n:25][c:14]2[NH:13][c:10]3[cH:11][cH:12][c:5]([c:7]([cH:9]3)[Cl:8])[F:6];2.1.2;Carboxylic"},{"depth":2,"reaction":{"label":"TTL ALL T5 UA ER ALL>>90","id":90},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MFESCIUQSIBMSM","smiles":"ClCCCBr","intrinsicScore":0.21,"id":90,"pathId":1918}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1918}],"RXN":"[CH2:1]=[CH:2][C:3](=[O:4])[NH:5][c:6]1[cH:11][c:10]2[c:9]([cH:8][c:7]1[OH:25])[n:24][cH:23][n:22][c:12]2[NH:13][c:14]3[cH:20][cH:19][c:17]([c:16]([cH:15]3)[Cl:21])[F:18].[CH2:26]([CH2:27][Cl:28])[CH2:29]Br>>[CH2:1]=[CH:2][C:3](=[O:4])[NH:5][c:6]1[cH:11][c:10]2[c:9]([cH:8][c:7]1[O:25][CH2:29][CH2:26][CH2:27][Cl:28])[n:24][cH:23][n:22][c:12]2[NH:13][c:14]3[cH:20][cH:19][c:17]([c:16]([cH:15]3)[Cl:21])[F:18];1.7.9;Williamson"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1918}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1918}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-8.403","depth":0,"reaction":{"label":">>0","id":0,"pathId":735},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.1,"literature":"[{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.0024762749671936035,\"rxn_id\":\"ord-9206c31e495e40198c626776f18ebc3a\",\"index\":585159,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COC(=O)[C@@H](C)[C@@H]1CCc2cc(O)ccc21.O.O=C([O-])[O-].[Cs+].[Cs+]>>COC(=O)[C@@H](C)[C@@H]1CCc2cc(OCCCBr)ccc21\",\"procedure_details\":\"Methyl (2S)-2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1 yl]propanoate (Example 14) (500 mg, 2.27 mmol), dibromopropane (4.308 g, 21.34 mmol), Cs2CO3 (834 mg, 2.56 mmol), and water (5 drops) were combined in DMF (20 mL) and stirred for 7 h at rt. The reaction mixture was concentrated under reduced pressure, water was added and the aqueous solution was extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc\\/hexane (v\\/v)=1:25) gave 263 mg (34%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 1.08 (d, 3H), 1.91 (m, 1H), 2.17 (m, 1H), 2.32 (m, 2H), 2.80 (m, 1H), 2.88 (m, 2H), 3.51 (m, 1H), 3.61 (t, 2H), 3.72 (s, 3H), 4.08 (t, 2H), 6.69 (d, 1H), 6.76 (s, 1H), 6.98 (d, 1H).\",\"reactant_000\":\"O=C([O-])[O-]\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"COC(=O)[C@@H](C)[C@@H]1CCc2cc(O)ccc21\",\"rxn_time\":7.0,\"reactant_003\":null,\"similarity\":0.9975237250328064,\"agent_000\":\"[Cs+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COC(=O)[C@@H](C)[C@@H]1CCc2cc(OCCCBr)ccc21\",\"rxn_str\":\"[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([C@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])[CH2:6][CH2:5]2.Br[C:18]([Br:21])([CH3:20])C.[C:22]([O-])([O-])=O.[Cs+].[Cs+]>O.CN(C=O)C>[Br:21][CH2:18][CH2:20][CH2:22][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([C@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])[CH2:6][CH2:5]2\",\"yield_000\":34.0},{\"solvent_000\":\"CCC(C)=O\",\"solvent_001\":null,\"distance\":0.0033658742904663086,\"rxn_id\":\"ord-53aae8a75c18456fa8b709f87e828e9f\",\"index\":589545,\"rxn_smiles\":\"CC(C)(Br)Br.CCC(C)=O.O=C([O-])[O-].Oc1ccc2c(c1)oc1cc(Cl)ccc12.[K+].[K+]>>Clc1ccc2c(c1)oc1cc(OCCCBr)ccc12\",\"procedure_details\":\"A mixture of 98.4 g (0.45 mole) of 7-chlorodibenzofuran-3-ol, 200 ml of methyl ethyl ketone, 93 g (0.67 mole) of potassium carbonate and 283 g (1.4 moles) of dibromopropane was refluxed for 24 hours. The inorganic precipitate was filtered off with suction and the filtrate was concentrated under reduced pressure. The residue was dissolved in 500 ml of methylene chloride and the solution was washed with 100 ml of water, 100 ml of 2 N sodium hydroxide solution and 100 ml of water in succession, dried over sodium sulfate and concentrated under reduced pressure. The solid residue was left to stand with 30 ml of pentane at 0° C. for 30 minutes, filtered off with suction and washed with 30 ml of cold n-pentane. 77 g of pure 1-bromo-3-(7-chlorodibenzofuran-3-oxy)-propane of melting point 83°-85° C. were obtained; yield: 50% of theory.\",\"reactant_000\":\"CC(C)(Br)Br\",\"reactant_002\":\"Oc1ccc2c(c1)oc1cc(Cl)ccc12\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9966341257095337,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Clc1ccc2c(c1)oc1cc(OCCCBr)ccc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:15]=[CH:14][C:5]2[C:6]3[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:7]=3[O:8][C:4]=2[CH:3]=1.[C:16](=O)([O-])[O-].[K+].[K+].Br[C:23]([Br:26])([CH3:25])C>C(C(C)=O)C>[Br:26][CH2:23][CH2:25][CH2:16][O:13][C:10]1[CH:11]=[CH:12][C:6]2[C:5]3[CH:14]=[CH:15][C:2]([Cl:1])=[CH:3][C:4]=3[O:8][C:7]=2[CH:9]=1\",\"yield_000\":50.4},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.003755807876586914,\"rxn_id\":\"ord-ad00632e1f604c52987b8464b6586244\",\"index\":429960,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COc1ccc(-c2cc(=O)c3ccc(O)cc3o2)cc1OC.O=C([O-])[O-].[Br-].[K+].[K+].[K+]>>COc1ccc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc1OC\",\"procedure_details\":\"This compound (61) was prepared from 3\\u2032,4\\u2032-dimethoxy-7-hydroxy-flavone, 27 (3 g, 10 mmol), dibromo propane (4 mL, 39.2 mmol) and potassium carbonate (2.8 g, 20 mmol) in dry dimethyl formamide (150 mL) using the identical procedure as described for 56. Yield 3.4 g (80%); mp 148-149° C.; MS (FAB) 419\\/421 (M++1); IR (KBr) 1630; 1H NMR (200 MHz, CDCl3) δ 8.12 (d, J=9.5 Hz, 1H), 7.53 (dd, J=8.5 Hz, 2.0 Hz, 1H), 7.36 (d, J=1.9 Hz, 1H), 6.99-6.95 (m, 3H), 6.68 (s, 1H), 4.24 (t, J=5.8 Hz, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 3.64 (t, J=6.3 Hz, 2H), 2.39 (q, J=6.1 Hz, 2H).\",\"reactant_000\":\"COc1ccc(-c2cc(=O)c3ccc(O)cc3o2)cc1OC\",\"reactant_002\":\"O=C([O-])[O-]\",\"reactant_001\":\"CC(C)(Br)Br\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962441921234131,\"agent_000\":\"[Br-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc1OC\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:6]1[O:7][C:8]2[C:13]([C:14](=[O:16])[CH:15]=1)=[CH:12][CH:11]=[C:10]([OH:17])[CH:9]=2.Br[C:24]([Br:27])([CH3:26])C.[C:28](=O)([O-])[O-].[K+].[K+].[K+].[Br-]>CN(C)C=O>[Br:27][CH2:24][CH2:26][CH2:28][O:17][C:10]1[CH:9]=[C:8]2[C:13]([C:14](=[O:16])[CH:15]=[C:6]([C:5]3[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:3]([O:2][CH3:1])[CH:4]=3)[O:7]2)=[CH:12][CH:11]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.0038167834281921387,\"rxn_id\":\"ord-8f37b80150c343f895cd5a9ba6cd0eb8\",\"index\":711891,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COc1cc(-c2cc(=O)c3ccc(O)cc3o2)cc(OC)c1OC.O=C([O-])[O-].[Br-].[K+].[K+].[K+]>>COc1cc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc(OC)c1OC\",\"procedure_details\":\"This compound (59) was prepared from 7-hydroxy-3\\u2032,4\\u2032,5\\u2032-trimethoxy-flavone, 25 (3.3 g, 10 mmol), dibromo propane (3 mL, 30 mmol) and potassium carbonate (2.7 g, 20 mmol) in dry dimethyl formamide (120 mL) using the identical procedure as described for 56. Yield 3.1 g (69%); mp 156-157° C.; MS (FAB) 449\\/451 (M++1); IR (KBr) 1629; 1H NMR (200 MHz, CDCl3) δ 8.13 (d, J=9.4 Hz, 1H), 7.11 (s, 2H), 7.01-6.97 (m, 2H), 6.70 (s, 1H), 4.25 (t, J=5.8 Hz, 2H), 3.96 (s, 6H), 3.93 (s, 3H), 3.64 (t, J=6.3 Hz, 2H), 2.39 (q, J=6.1 Hz, 2H).\",\"reactant_000\":\"COc1cc(-c2cc(=O)c3ccc(O)cc3o2)cc(OC)c1OC\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961832165718079,\"agent_000\":\"[Br-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc(OC)c1OC\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[CH:7]=[C:8]([C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[O:9]2)=[CH:4][CH:3]=1.Br[C:26]([Br:29])([CH3:28])C.[C:30](=O)([O-])[O-].[K+].[K+].[K+].[Br-]>CN(C)C=O>[Br:29][CH2:26][CH2:28][CH2:30][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[CH:7]=[C:8]([C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[O:9]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CC(=O)OC(C)C\",\"distance\":0.003999054431915283,\"rxn_id\":\"ord-6b7ff184146e44f58a563b737ef5d8b3\",\"index\":342812,\"rxn_smiles\":\"CC(=O)OC(C)C.CC(C)(Br)Br.CCCc1c(O)ccc2c(CC)noc12.CN(C)C=O.O=C([O-])[O-].[Cs+].[Cs+]>>CCCc1c(OCCCBr)ccc2c(CC)noc12\",\"procedure_details\":\"A solution of 3-ethyl-6-hydroxy-7-propylbenz[4,5]isoxazole (2.00 grams; 9.74 mmol) in dry DMF was treated with dibromopropane (7.17 mL; 38.97 mmol) and cesium carbonate (3.49 grams; 10.71 mmol). The solution was stirred at room temperature for 10 hours, then partioned between isopropyl acetate and pH 4.0 buffer. The organic layer was washed twice with water, dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel chromatography afforded the title compound (1.74 g).\",\"reactant_000\":\"CCCc1c(O)ccc2c(CC)noc12\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9960009455680847,\"agent_000\":\"[Cs+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CCCc1c(OCCCBr)ccc2c(CC)noc12\",\"rxn_str\":\"[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][C:10]([OH:15])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][N:4]=1)[CH3:2].Br[C:17]([Br:20])([CH3:19])C.[C:21](=O)([O-])[O-].[Cs+].[Cs+].C(OC(C)C)(=O)C>CN(C=O)C>[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][C:10]([O:15][CH2:21][CH2:19][CH2:17][Br:20])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][N:4]=1)[CH3:2]\",\"yield_000\":54.8}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":735}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":735}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":735}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":735}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.7,"id":154,"pathId":735}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":5,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>491","id":491},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KQNBBQSOHFVNDL","smiles":"CC(C)(O)Br","intrinsicScore":0.7,"id":491,"pathId":735}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":735}],"RXN":"CC(C)(O)Br.c1cc(c(cc1Nc2c3cc(c(cc3ncn2)O)[N+](=O)[O-])Cl)F>>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCBr)[N+](=O)[O-])Cl)F;0.0;Unrecognized"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":735}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":735}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":735}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":735}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":735}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":735}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.425","depth":0,"reaction":{"label":">>0","id":0,"pathId":160},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.6,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.008023500442504883,\"rxn_id\":\"ord-42dc5bd007e148f297483fd574a84112\",\"index\":514864,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCN(CC)CC.Cl.Cl.N#Cc1ccc(Cn2cncc2CCN)cc1F>>N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride (0.92 g, 0.0029 mmol) in acetonitrile (150 mL) and triethylamine (3.2 mL) was added 2-bromoethyl ether (0.839 mL, 0.0067 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in uacuo and the residue was dissolved in EtOAc which was washed twice with 1M HCl (100 mL). The HCl layers were combined and adjusted to pH=9 with solid Na2CO3 and extraxcted 3 times with EtOAc. The EtOAc layers were combined and dried with brine and MgSO4. Removal of the EtOAc in vacuo yielded the title compound which was used as is in the next step.\",\"reactant_000\":\"N#Cc1ccc(Cn2cncc2CCN)cc1F\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919764995574951,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=2)[CH:9]=[N:8][CH:7]=1.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>C(#N)C.C(N(CC)CC)C>[F:20][C:14]1[CH:13]=[C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][N:3]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:7][N:8]=[CH:9]2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.008291244506835938,\"rxn_id\":\"ord-08bb54aa0ab244ff90317c31f9d4c5e8\",\"index\":731783,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.NC1CCN(Cc2ccccc2)CC1.O=C([O-])[O-].[K+].[K+]>>c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"procedure_details\":\"To a stirred mixture of 4-amino-1-benzylpiperidine (1.53 mL, 7.5 mmol), K2CO3 (2.28 g, 16.5 mmol) and DMF (15 mL) heated at 50° C. was added dropwise over 60 min bis(2-bromoethyl) ether (0.96 mL, 7.65 mmol). After stirring for 6 hours at 80° C., the solvent was removed by blowing with a stream of nitrogen over 2 hours. The residue was purified on a silica gel column to give 1.7 g (87%) of 4-(1-benzyl-piperidin-4-yl)morpholine as a waxy solid.\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"NC1CCN(Cc2ccccc2)CC1\",\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9917087554931641,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"rxn_str\":\"[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>CN(C=O)C>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:1]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1\",\"yield_000\":87.1},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.008305191993713379,\"rxn_id\":\"ord-ac7a693c46694fd5b13039f5c104d79e\",\"index\":134482,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N.O=C([O-])[O-].[K+].[K+]>>CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"procedure_details\":\"cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane\\/methanol\\/ammonia 100:0:0->140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m\\/e=403.3 [(M+H)+].\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9916948080062866,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"rxn_str\":\"[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]\",\"yield_000\":68.6},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.00859677791595459,\"rxn_id\":\"ord-aa3eb88c8e6c445794e16d41429514f0\",\"index\":719114,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O.CCN(CC)CC.Cl.Cl>>CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-2-methyl-imidazol-1-ylmethyl]-2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile dihydrochloride (as described in Example 11) (0.25 g, 0.456 mmol) in acetonitrile (35.0 mL) and triethylamine (1.8 mL) was added 2-bromoethyl ether (0.133 mL, 1.06 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in vacuo to obtain the title compound after purification by preparative HPLC.\",\"reactant_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9914032220840454,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]4([CH2:36][CH3:37])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]4=[O:35])[CH:22]=3)[CH:13]=2)[C:9]([CH3:38])=[N:8][CH:7]=1.Br[CH2:40][CH2:41][O:42][CH2:43][CH2:44]Br>C(#N)C.C(N(CC)CC)C>[CH2:36]([C:27]1([C:23]2[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=2)[O:20][C:14]2[CH:13]=[C:12]([CH2:11][N:10]3[C:6]([CH2:5][CH2:4][N:3]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[CH:7][N:8]=[C:9]3[CH3:38])[CH:19]=[CH:18][C:15]=2[C:16]#[N:17])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]1=[O:35])[CH3:37]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.008690357208251953,\"rxn_id\":\"ord-90e436a959164d40ab8c094946564425\",\"index\":740936,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.Nc1ccc(Br)c(Cl)c1.O.O=C([O-])[O-].[I-].[K+].[K+].[K+]>>Clc1cc(N2CCOCC2)ccc1Br\",\"procedure_details\":\"4-Bromo-3-chloroaniline (500 mg) was dissolved in DMF (10 ml), and bis(2-bromoethyl)ether (1.12 g), K2CO3 (1.34 g), and potassium iodide (80 mg) were added thereto, followed by stirring at 80° C. for 2 days. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 20% EtOAc\\/hexane) to obtain 4-(4-bromo-3-chlorophenyl)morpholine (263 mg).\",\"reactant_000\":\"Nc1ccc(Br)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":48.0,\"reactant_003\":null,\"similarity\":0.991309642791748,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[I-]\",\"agent_002\":\"[K+]\",\"temperature\":80.0,\"product_000\":\"Clc1cc(N2CCOCC2)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:9].Br[CH2:11][CH2:12][O:13][CH2:14][CH2:15]Br.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][C:3]=1[Cl:9]\",\"yield_000\":39.3}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":\"CCO\",\"distance\":0.0034121274948120117,\"rxn_id\":\"ord-c978110d0ebb47c5ab077decdb013eb8\",\"index\":750238,\"rxn_smiles\":\"CCO.CP(C)C.[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1.[NH4+].[OH-].c1ccncc1>>NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"procedure_details\":\"To a solution of (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 0.230 mmol) in pyridine (2 mL) was added NH4OH (200 μl) and trimethylphosphine (344 μl, 0.344 mmol) sequentially at room temperature. The reaction mixture was stirred for 2 h. After EtOH (1 mL) was added, the reaction mixture was concentrated in vacuo. The crude product was purified by flash chromatography (20% MeOH in DCM containing 0.5% NH3\\/DCM) to provide 89.6 mg of (S)\\u2014N-(2-amino-1-(3-chloro-5-fluorophenyl)ethyl)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamide (79%). LCMS (m\\/z): 488.2 (MH+), 0.66 min. 1H NMR (500 MHz, METHANOL-d4) δ ppm 7.98-7.89 (m, 1H), 7.89-7.79 (m, 1H), 7.74 (td, J=1.4, 8.0 Hz, 1H), 7.69-7.61 (m, 1H), 7.41-7.28 (m, 1H), 7.27-7.08 (m, 2H), 5.27-5.12 (m, 1H), 4.07 (dd, J=3.8, 11.0 Hz, 2H), 3.69-3.52 (m, 2H), 3.14-3.03 (m, 2H), 2.96 (tt, J=3.9, 11.7 Hz, 1H), 2.02-1.77 (m, 4H).\",\"reactant_000\":\"[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996587872505188,\"agent_000\":\"CP(C)C\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]([C:14]2[CH:35]=[CH:34][C:17]([C:18]([NH:20][C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=3)[CH2:22][N:23]=[N+]=[N-])=[O:19])=[C:16]([F:36])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[NH4+].[OH-].CP(C)C.CCO>N1C=CC=CC=1>[NH2:23][CH2:22][C@@H:21]([NH:20][C:18](=[O:19])[C:17]1[CH:34]=[CH:35][C:14]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([CH:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:4]=2)=[CH:15][C:16]=1[F:36])[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=1\",\"yield_000\":79.8},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004088282585144043,\"rxn_id\":\"ord-042249e7216a47579d0f62148c807cd2\",\"index\":714256,\"rxn_smiles\":\"C1CCOC1.C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21>>NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"procedure_details\":\"20 μL of a 1M trimethylphosphine\\/tetrahydrofuran solution was added to 6 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-azidoethyl) ester dissolved in a mixture of 0.15 mL of tetrahydrofuran and 0.02 mL of water at room temperature, and the mixture was stirred for 13 hours. After the solvent was distilled under reduced pressure, the residue was purified by reverse phase column chromatography (Wako gel 50C18 (made by Wako Pure Chemical Industries Ltd.), eluent: water to a 50% aqueous solution of acetonitrile), and the obtained solids were further washed with tetrahydrofuran, thereby yielding 2 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-aminoethyl)ester.\",\"reactant_000\":\"[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":13.0,\"reactant_003\":null,\"similarity\":0.995911717414856,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"rxn_str\":\"CP(C)C.O1CCCC1.[N:10]([CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17])=[N+]=[N-]>O1CCCC1.O>[NH2:10][CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17]\",\"yield_000\":35.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0043354034423828125,\"rxn_id\":\"ord-d978c1c7e23041a1b604dc1dd6ff7a6f\",\"index\":562746,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1>>NCc1cncc(C#Cc2ccccc2)c1\",\"procedure_details\":\"To a solution of 3-(azidomethyl)-5-(phenylethynyl)pyridine (7.8 g, 33.3 mmol) in tetrahydrofuran (101 mL) at 0° C. was added trimethylphosphine (1M in tetrahydrofuran, 49.9 mL, 49.9 mmol). After evolution of nitrogen had slowed, the ice bath was removed and stirring continued for 1 h. To this was added water (6.0 mL, 333 mmol) and the mixture stirred at room temperature for 2 h. The reaction was concentrated, dissolved in ether, washed with water (5×), then brine, dried over potassium carbonate, filtered, and concentrated to give 5.96 g (77%) as a faint yellow solid which was used without purification. 1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H)1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H). 13C NMR (CDCl3) δ: 150.8, 147.9, 137.8, 137.4, 131.8, 128.9, 128.6, 122.7, 120.3, 92.7, 86.1, 43.7. Mass spec.: 209.1 (MH)+.\",\"reactant_000\":\"[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9956645965576172,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCc1cncc(C#Cc2ccccc2)c1\",\"rxn_str\":\"[N:1]([CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[N+]=[N-].CP(C)C.O>O1CCCC1>[C:13]1([C:12]#[C:11][C:9]2[CH:10]=[C:5]([CH2:4][NH2:1])[CH:6]=[N:7][CH:8]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.005223870277404785,\"rxn_id\":\"ord-089f68b08fe543bfbdedd8c9521524ae\",\"index\":377104,\"rxn_smiles\":\"C1COCCO1.CP(C)C.O.[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21>>NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"procedure_details\":\"Azide 23 (Example 10, 100 mg, 0.23 mmol) is dissolved in 0.9 mL of 1,4-dioxane\\/H2O (8:1), and 0.3 mL of a trimethylphospine solution (1 M in THF) is added. The reaction is stirred at room temperature for 3 h, then all volatiles are removed in vacuo. The crude product is purified by flash column chromatography with dichloromethane\\/methanol (95:5 to 10:1). Yield: 87 mg (0.021 mmol, 91%).\",\"reactant_000\":\"[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9947761297225952,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"rxn_str\":\"[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][N:14]=[N+]=[N-])=[C:4]([O:17][CH2:18][C:19]2[CH:32]=[CH:31][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)[N:3]=1.CP(C)C>O1CCOCC1.O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][NH2:14])=[C:4]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:27])([F:29])[F:28])=[CH:31][CH:32]=2)[N:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.005546689033508301,\"rxn_id\":\"ord-be83b62c5d5249cf938c714d7117d666\",\"index\":193745,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1>>NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"procedure_details\":\"To a solution of (S)-2-[[1-(2-azidoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid (6.28 g, 12.11 mmol) in THF (91 mL) was added a solution of trimethylphosphine in THF (48.5 mL, 48.46 mmol, 1.0M) at 0° C. It was a clear solution in the beginning and after 30 min some precipitate was formed and this mixture was stirred for overnight at which time TLC analysis of the mixture indicated the absence of starting material. Then, 10 equiv. of water (120 mmol, 2.16 mL) was added and the mixture was stirred for 2 h at room temperature. The solvent was removed under vacuum and the residue was azeotrophed two times with toluene to give a pasty material which was purified using HPLC to obtain 4.57 g (77% yield) of (S)-2-[[1-(2-aminoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid as an amorphous white solid. ES(+)-HRMS m\\/e calcd. for C24H27Cl2N3O4 (M+H)+ 492.1452, obsd. 492.1451.\",\"reactant_000\":\"[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9944533109664917,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"rxn_str\":\"[N:1]([CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:21][CH:20]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:23][CH:24]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1\",\"yield_000\":76.6}]","literatureScore":1,"label":"TTL ALL>>167","id":167},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008967578411102295,\"rxn_id\":\"ord-cf2e4e3955c04b01a2130e020e40723c\",\"index\":264007,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-4-fluorophenylamine (1.67 g, 4.87 mmoles) and sodium azide (0.38 g, 5.84 mmoles) in DMSO (20 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (1.44 g, 4.14 mmoles).\",\"reactant_000\":\"Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9910324215888977,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([O:18][CH2:19][CH2:20]Cl)[C:12]=2[NH2:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>CS(C)=O.O>[N:23]([CH2:20][CH2:19][O:18][C:13]1[CH:14]=[C:15]([F:17])[CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:22])=[N+:24]=[N-:25]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CCOC(C)=O\",\"distance\":0.00959622859954834,\"rxn_id\":\"ord-693a2494d2a64d6e84f87595007867e9\",\"index\":765833,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc(OCCCCl)cc1CO.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"procedure_details\":\"DMF (7.5 mL) was added to (5-(3-chloropropoxy)-2-nitrophenyl)methanol (635 mg, 0.00258 moles) and sodium azide (252 mg, 0.00387 moles) in a flask, and the resulting mixture was heated to 70° C. and stirred overnight. The reaction was diluted in ethyl acetate (100 mL) and washed twice with water (75 mL each) and once with brine (75 mL). The organic layer was dried with anhydrous magnesium sulfate, which was filtered out. The filtrate was concentrated on a rotary evaporator and dried in vacuo overnight to yield (5-(3-azidopropoxy)-2-nitrophenyl)methanol as a yellow solid (yield 88%). H NMR (400 MHz, CD2Cl2) δ 8.16 (d, J=9.1 Hz, 1H), 7.27 (d, J=2.8 Hz, 1H), 6.91 (dd, J=9.1, 2.8 Hz, 1H), 4.98 (s, 2H), 4.18 (t, J=6.0 Hz, 2H), 3.53 (t, J=6.6 Hz, 2H), 2.12-2.06 (m, 2H). 13C-NMR (100 MHz, CD2Cl2) δ 163.99, 141.22, 128.43, 114.97, 113.93, 66.15, 63.26, 48.68, 29.13 HRMS m\\/z: calculated for C10H12N4O4 [M+H]+, 253.0931. found, 253.0939.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCCCCl)cc1CO\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9904037714004517,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"rxn_str\":\"CN(C=O)C.Cl[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>C(OCC)(=O)C>[N:22]([CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1)=[N+:23]=[N-:24]\",\"yield_000\":88.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CS(C)=O\",\"distance\":0.009707868099212646,\"rxn_id\":\"ord-ed6541dc83464b24a92f34950c9068d0\",\"index\":137604,\"rxn_smiles\":\"CS(C)=O.O.O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"procedure_details\":\"A mixture of 6-(2-chloro-ethoxy)-3-(naphthalene-1-sulfonyl)-1-H-indazole (0.19 g, 0.5 mmoles) and sodium azide (0.04 g, 0.62 mmoles) in DMSO (2 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.17 g, 0.45 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9902921319007874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1.[N-:27]=[N+:28]=[N-:29].[Na+]>CS(C)=O.O>[N:27]([CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1)=[N+:28]=[N-:29]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.010035336017608643,\"rxn_id\":\"ord-dc8e8747d9b6443687f6f629e49ca7d3\",\"index\":120480,\"rxn_smiles\":\"CN(C)C=O.Nc1ncnc2c1ncn2CCCCl.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"procedure_details\":\"A mixture of 9-(3-chloropropyl)adenine and sodium azide in DMF was stirred at 80° C. for 24 hours, cooled to room temperature and filtered. The solid was washed with CH2Cl2. The solvent was removed from the combined filtrates and the residue was taken up in water with sonication. The aqueous layer was extracted with CH2Cl2. After removing the solvent, the crude product was recrystallized from ethanol to give 9-(3-azidopropyl)adenine as a white crystalline solid.\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1ncnc2c1ncn2CCCCl\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9899646639823914,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14].[N-:15]=[N+:16]=[N-:17].[Na+]>CN(C=O)C>[N:15]([CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14])=[N+:16]=[N-:17]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.010115861892700195,\"rxn_id\":\"ord-5c4de244180f41a2bbc87a484238a728\",\"index\":335449,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-phenylamine (0.5 g, 1.53 mmoles) and sodium azide (0.15 g, 2.29 mmoles) in DMSO (10 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.39 g, 1.17 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9898841381072998,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19]Cl)[C:12]=2[NH2:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>CS(C)=O.O>[N:22]([CH2:19][CH2:18][O:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:21])=[N+:23]=[N-:24]\",\"yield_000\":null}]","literatureScore":0.99,"label":"ER UA TTL ALL>>672","id":672},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":6,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":8,"reaction":{"label":"AT T5 ER UA 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ALL>>51","id":51},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"FOZVXADQAHVUSV","smiles":"BrCCOCCBr","intrinsicScore":0.051,"id":51,"pathId":160}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":160}],"RXN":"[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][NH2:8])[N+:30](=[O:31])[O-:32])[Cl:29])[F:26].[CH2:2]([CH2:1]Br)[O:3][CH2:4][CH2:5]Br>N#CC.[O-]C(=O)[O-].[I-].[K+]>[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][N:8]4[CH2:1][CH2:2][O:3][CH2:4][CH2:5]4)[N+:30](=[O:31])[O-:32])[Cl:29])[F:26];4.2.5;Morpholine"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":160}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 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ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":160}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":160}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.457","depth":0,"reaction":{"label":">>0","id":0,"pathId":287},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":6,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":287}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":287}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":287}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":287}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":287}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":4,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":287}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":287}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":287}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":287}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":287}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":287}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":287}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.473","depth":0,"reaction":{"label":">>0","id":0,"pathId":1867},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":null,\"distance\":0.0018466711044311523,\"rxn_id\":\"ord-fcb42d8f2e554416b625a3eb41c8acb6\",\"index\":263752,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1>>C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"procedure_details\":\"4-(3-Aminophenyl)-2-chloro-N-(3-fluorophenyl)pyrimidin-5-amine (15 mg, 0.048 mmol) was added to a solution of acryloyl chloride (4.24 μL, 0.052 mmol) in the presence of triethylamine (0.013 mL, 0.095 mmol) at 0° C., and the reaction mixture was stirred for 12 h at rt. The reaction was monitored by TLC. After completion of the reaction, the compound was purified by column chromatography to give the title compound (3.26 mg, 16% yield). ESI-MS: m\\/z 369.09 [M+H]+.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_time\":12.0,\"reactant_003\":null,\"similarity\":0.9981533288955688,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(-c2nc(Cl)ncc2Nc2cccc(F)c2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[CH:12][N:11]=[C:10]([Cl:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].C(N(CC)CC)C>>[Cl:22][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:26])[CH:24]=[CH2:25])[CH:7]=[CH:6][CH:5]=2)[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[CH:12][N:11]=1\",\"yield_000\":18.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0026835203170776367,\"rxn_id\":\"ord-417509d1b40c4e22819fd3234a86a41e\",\"index\":159438,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1>>C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"procedure_details\":\"Acryloyl chloride was reacted with 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline in THF, at 0° C. The final product was obtained in quantitative yield.\",\"reactant_000\":\"C=CC(=O)Cl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973164796829224,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1ccc2ncnc(Nc3cc(Cl)c(Cl)cc3F)c2c1\",\"rxn_str\":\"[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH2:26])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:1](=[O:4])[CH:2]=[CH2:3])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[C:10]([F:14])=[CH:11][C:12]=1[Cl:13]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.003296792507171631,\"rxn_id\":\"ord-684c4ec13b2641b880cea229e63cb756\",\"index\":286413,\"rxn_smiles\":\"C=CC(=O)Cl.CCN(CC)CC.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"procedure_details\":\"To a stirred solution of N4-(3-aminophenyl)-N6-(3-phenoxyphenyl)pyrimidine-4,6-diamine (40 mg, 0.1 mmol), Et3N (0.03 mL, 0.2 mmol) and NMP (0.4 mL) in CH2Cl2 (2 mL), at 0° C., was added acryloyl chloride (6) (29 mg, 0.3 mmol). The reaction mixture was allowed to come to rt and stirred at this temperature for 3 h. It was washed with 10% NaHCO3 solution (2 mL), water (2 mL), brine (2 mL) and dried over Na2SO4. Filtration followed by concentration under reduced pressure offered a residue which was purified by column chromatography (SiO2, 230-400, chloroform\\/methanol, 9\\/1) to gave N-(3-(6-(3-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (I-75) as a light brown solid. 1H NMR (DMSO-d6) δ ppm: 5.73 (dd, J=1.72 & 10 Hz, 1H), 6.18 (s, 1H), 6.24 (dd, J=1.92 & 17 Hz, 1H), 6.45 (dd, J=10.04 & 16.88 Hz, 1H), 6.54-6.57 (m, 1H), 7.01-7.05 (m, 2H), 7.11-7.15 (dd, J=0.88 & 7.48 Hz, 1H), 7.19-7.32 (s, 4H), 7.35-7.41 (m, 4H), 7.89 (s, 1H), 8.26 (s, 1H), 9.2 (s, 1H), 9.25 (s, 1H), 10.26 (s, 1H); LCMS: m\\/e 423.8 (M+1).\",\"reactant_000\":\"CN1CCCC1=O\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9967032074928284,\"agent_000\":\"C=CC(=O)Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Oc4ccccc4)c3)ncn2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.CN1[C:41](=[O:42])[CH2:40][CH2:39]C1.C(Cl)(=O)C=C>C(Cl)Cl>[O:22]([C:18]1[CH:17]=[C:16]([NH:15][C:13]2[N:12]=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH:40]=[CH2:39])[CH:7]=[CH:6][CH:5]=3)[CH:14]=2)[CH:21]=[CH:20][CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)N(C)C\",\"solvent_001\":null,\"distance\":0.0033723115921020508,\"rxn_id\":\"ord-d2553819a2544c32acf3e419993c21f7\",\"index\":434821,\"rxn_smiles\":\"C=CC(=O)Cl.CC(=O)N(C)C.Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O>>C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"procedure_details\":\"A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0° C. in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol\\/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g).\",\"reactant_000\":\"Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.996627688407898,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C=CC(=O)Nc1ccc(CN\\/C=C2\\\\C(=O)NC(=O)c3ccc(I)cc32)cc1O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)=[CH:4][C:3]=1[OH:24].[C:25](Cl)(=[O:28])[CH:26]=[CH2:27]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:6][NH:7]\\/[CH:8]=[C:9]2\\\\[C:10](=[O:21])[NH:11][C:12](=[O:20])[C:13]3[C:18]\\\\2=[CH:17][C:16]([I:19])=[CH:15][CH:14]=3)[CH:22]=[CH:23][C:2]=1[NH:1][C:25](=[O:28])[CH:26]=[CH2:27]\",\"yield_000\":142.2},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.0033959150314331055,\"rxn_id\":\"ord-cf8d7a128a39495c876d27a1c2bb274c\",\"index\":662786,\"rxn_smiles\":\"C1CCOC1.C=CC(=O)Cl.CCN(CC)CC.Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1>>C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"procedure_details\":\"A solution of 3-[6-(3-bromophenylamino)-pyrimidin-4-ylamino]phenylamine (250 mg, 0.7 mmol) and triethylamine (180 mg, 1.75 mmol) in 5 mL of THF was stirred at RT. Acryloyl chloride (80 mg, 0.9 mmol) was added into the reaction mixture and it was stirred at RT for 1 h. The solvent was removed by vacuum evaporation and the crude product was purified by flash chromatography on silica gel with EtOAc\\/DCM solvent system to afford 115 mg (40% yield) of the title compound as a light colored solid. MS (m\\/z): MH+=410, 412. 1H NMR (DMSO): 10.15 (s, 1H), 9.36 (s, 1H), 9.28 (s, 1H), 8.34 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 7.51-7.11 (m, 5H), 6.47 (dd, 1H, J1=10.1 Hz, J2=17.0 Hz), 6.27 (dd, 1H, J1=1.9 Hz, J2=17.0 Hz), 6.20 (s, 1H), 5.76 (dd, 1H, J1=10.1 Hz, J2=1.9 Hz) ppm.\",\"reactant_000\":\"Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"reactant_002\":null,\"reactant_001\":\"C=CC(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9966040849685669,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=CC(=O)Nc1cccc(Nc2cc(Nc3cccc(Br)c3)ncn2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22][C:30](=[O:33])[CH:31]=[CH2:32])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1\",\"yield_000\":40.0}]","literatureScore":1,"label":"AT UA ER ALL>>15","id":15},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005068659782409668,\"rxn_id\":\"ord-67cd89c92ec043eaa8c192a52c6055e1\",\"index\":71209,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)c(F)c2)cc1>>N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"procedure_details\":\"The product from Example 167A and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (99% yield). 1HNMR (300 MHz, CDCl3) δ2.30 (m, 2H), 3.80 (m, 2H), 4.25 (m, 2H), 7.12-7.75 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)c(F)c2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9949313402175903,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)=[CH:3][C:2]=1[F:1]\",\"yield_000\":99.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005764007568359375,\"rxn_id\":\"ord-593d5907c892416383020940bf139801\",\"index\":592545,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)cc2)cc1F>>N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"procedure_details\":\"The product from Example 166B and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (98% yield). 1HNMR (300 MHz, CDCl3) δ2.25 (m, 2H), 3.80 (m, 2H), 4.20 (m, 2H), 7.00-7.65 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)cc2)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9942359924316406,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([F:1])[CH:3]=2)=[CH:11][CH:12]=1\",\"yield_000\":98.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00615382194519043,\"rxn_id\":\"ord-0943760d2d71451cb76c1188d0d02866\",\"index\":410217,\"rxn_smiles\":\"ClCCCBr.O=C1NCCn2c1cc1cc(O)cnc12>>O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"procedure_details\":\"The title compound was synthesized in analogy to example 2, intermediate, from 7-hydroxy-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one (example 84, intermediate a) and 1-bromo-3-chloropropane, to give the desired product as a light yellow solid (80%).\",\"reactant_000\":\"O=C1NCCn2c1cc1cc(O)cnc12\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9938461780548096,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"rxn_str\":\"[OH:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1\",\"yield_000\":80.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.006797671318054199,\"rxn_id\":\"ord-f2089ee29c9c49d6bda509b96fde9e15\",\"index\":355059,\"rxn_smiles\":\"ClCCCBr.Cn1ncc(-c2ccc(O)cc2)cc1=O>>Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"procedure_details\":\"5-[4-(3-Chloro-propoxy)-phenyl]-2-methyl-2H-pyridazin-3-one was prepared from 5-(4-hydroxy-phenyl)-2-methyl-2H-pyridazin-3-one with 1-bromo-3-chloro-propane using the procedure described in Example 86 Step 3; Mp 90-91° C.; MS m\\/z 279 (M+H).\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"Cn1ncc(-c2ccc(O)cc2)cc1=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9932023286819458,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.007008194923400879,\"rxn_id\":\"ord-cbbf3a06c7d04efaab9b011975b2bcaf\",\"index\":118810,\"rxn_smiles\":\"CC(C)=O.ClCCCBr.O=C1CSc2cc(O)ccc2N1>>O=C1CSc2cc(OCCCCl)ccc2N1\",\"procedure_details\":\"After a mixture consisting of 7-hydroxy-3,4-dihydro-2H-1,4-benzothiazin-3-one (1.812 g, 10 mmol), 1bromo-3-chloropropane (2.362 g, 15 mmol), potassium carbate (4.146 g, 30 mmol) and acetone (40 mmol) was heated under reflux and stirring for 24 hours, insolube matter was filtered off, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel column (developer: chloroform) to purify the same, and was then recrystallized from acetone. The title compound (1.300 g) was obtained as yellow leaflets (yield: 50.4%).\",\"reactant_000\":\"O=C1CSc2cc(O)ccc2N1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9929918050765991,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CSc2cc(OCCCCl)ccc2N1\",\"rxn_str\":\"[OH:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.Br[CH2:14][CH2:15][CH2:16][Cl:17].CC(C)=O>>[Cl:17][CH2:16][CH2:15][CH2:14][O:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1\",\"yield_000\":50.4}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002769649028778076,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9972303509712219,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0031270384788513184,\"rxn_id\":\"ord-dcc1a5efa86d4d09b08ec14f86ec1748\",\"index\":264188,\"rxn_smiles\":\"Cl.O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12>>Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"procedure_details\":\"A solution of stannous chloride dihydrate (3.7 g, 16 mmol) in 10 ml of conc. hydrochloric acid was added dropwise to a stirred suspension of 2,3-dihydroxy-6-nitrobenzo(f)quinoxaline (1.3 g, 5 mmol) in 8 ml of conc. hydrochloric acid. Then the mixture was stirred at 60-70° C. on an oil bath for 2 h. After cooling on ice, the precipitate was collected, dissolved in boiling water (1 1), filtered while hot, and neutralized to pH 6 with solid sodium hydrogen carbonate. The yellow product was isolated and recrystallized from DMF\\/water, washed with water, ethanol and ether and finally dried at 110 ° C. to give 0.90 g (63%) of pure title compound, m.p. >300° C., IR (KBr): 1690, ? 1640 and 1605 cm-1,1H-NMR (DMSO-d6): 5.8 (broad s, 2H,NH2), 6.63(s,1H, H-5), 7.2-8.7 (m, 4H, ArH), 11.8 (broad s, 2H, 20H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968729615211487,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([OH:19])=[N:4][C:5]2[CH:6]=[C:7]([N+:16]([O-])=O)[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[N:11]=1>Cl>[NH2:16][C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]2[N:11]=[C:2]([OH:1])[C:3]([OH:19])=[N:4][C:5]=2[CH:6]=1\",\"yield_000\":79.2},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.00328141450881958,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9967185854911804,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003656148910522461,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963438510894775,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003899812698364258,\"rxn_id\":\"ord-fc93af0f0d9a40e284c2500298acaf93\",\"index\":573049,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"The crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine was dissolved in THF and reduced using Raney nickel catalyst to yield N4-(3-Chloro-4-fluoro-phenyl)-7-(2,2-difluoro-ethoxy)-quinazoline-4,6-diamine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961001873016357,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C1COCC1.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null}]","literatureScore":1,"label":"UA CF T5 AT ER TTL ALL>>33","id":33},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1867}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1867}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":1867}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":1867}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.68,"id":154,"pathId":1867}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEFNIUDZICAGOU","smiles":"NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1O","intrinsicScore":0.16,"id":33,"pathId":1867}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[N+:21](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[NH2:21])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"TTL ALL T5 UA ER ALL>>90","id":90},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MFESCIUQSIBMSM","smiles":"ClCCCBr","intrinsicScore":0.16,"id":90,"pathId":1867}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.75,"id":34,"pathId":1867}],"RXN":"[cH:14]1[cH:13][c:12]([c:10]([cH:9][c:8]1[NH:7][c:6]2[c:5]3[cH:19][c:1]([c:2]([cH:3][c:4]3[n:18][cH:17][n:16]2)[OH:20])[NH2:21])[Cl:11])[F:15].[CH2:23]([CH2:24][Cl:25])[CH2:22]Br>>[cH:14]1[cH:13][c:12]([c:10]([cH:9][c:8]1[NH:7][c:6]2[c:5]3[cH:19][c:1]([c:2]([cH:3][c:4]3[n:18][cH:17][n:16]2)[O:20][CH2:22][CH2:23][CH2:24][Cl:25])[NH2:21])[Cl:11])[F:15];1.7.9;Williamson"},{"depth":2,"reaction":{"label":"T5 ER UA ALL>>7","id":7},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HFBMWMNUJJDEQZ","smiles":"ClC(=O)C=C","intrinsicScore":0.75,"id":7,"pathId":1867}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WIZMQMNKZUGGHO","smiles":"FC1=CC=C(NC2=NC=NC3=C2C=C(NC(=O)C=C)C(OCCCCl)=C3)C=C1Cl","intrinsicScore":0.061,"id":15,"pathId":1867}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])Cl.[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:16]2[c:17]3[cH:18][c:19]([c:10]([cH:11][c:12]3[n:13][cH:14][n:15]2)[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[NH2:20])[Cl:29])[F:26]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:20][c:19]1[cH:18][c:17]2[c:12]([cH:11][c:10]1[O:5][CH2:6][CH2:7][CH2:8][Cl:9])[n:13][cH:14][n:15][c:16]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:27]([cH:28]3)[Cl:29])[F:26];2.1.1;Amide"},{"depth":1,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.061,"id":9,"pathId":1867}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1867}],"RXN":"[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8]Cl)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]3[cH:22][cH:23][c:24]([c:26]([cH:28]3)[Cl:27])[F:25].[CH2:30]1[CH2:31][O:32][CH2:33][CH2:34][NH:29]1>>[CH2:14]=[CH:13][C:11](=[O:12])[NH:10][c:9]1[cH:15][c:1]2[c:2]([cH:3][c:4]1[O:5][CH2:6][CH2:7][CH2:8][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[n:16][cH:17][n:18][c:19]2[NH:20][c:21]4[cH:22][cH:23][c:24]([c:26]([cH:28]4)[Cl:27])[F:25];1.6.4;Chloro"},{"pathScore":"-8.497","depth":0,"reaction":{"label":">>0","id":0,"pathId":217},"children":[{"depth":1,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.3,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":null,\"distance\":0.042360901832580566,\"rxn_id\":\"ord-105c1b9741f548d78652c923698b9661\",\"index\":767089,\"rxn_smiles\":\"CCOC(=O)N1C=Cc2c(oc3c(Cl)cc(Br)cc23)CC1.CC[SiH](CC)CC.O=C(O)C(F)(F)F>>CCOC(=O)N1CCc2oc3c(Cl)cc(Br)cc3c2CC1\",\"procedure_details\":\"To a solution of the product of step C (50 mg, 0.13 mmol) and trifluoroacetic acid (0.75 mL) at 0° C. was added triethylsilane (64 μL, 0.40 mmol). The reaction was allowed to warm to ambient temperature over 14 h then quenched by addition of aqueous sodium bicarbonate solution. The mixture was extracted with dichloromethane (2×20 mL) and the combined organic extracts dried over anhydrous Na2SO4, filtered, and the filtrate concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 9:1 to 1:1 hexanes\\/ethyl acetate) to give ethyl 9-bromo-7-chloro-4,5-dihydro-1H-benzofuro[2,3-d]azepine-3(2H)-carboxylate (48 mg, 96%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.45-7.38 (m, 1H), 7.35 (d, J=1.4 Hz, 1H), 4.20 (q, J=7.1 Hz, 2H), 3.78-3.67 (m, 4H), 3.20-3.10 (m, 2H), 2.88-2.75 (m, 2H), 1.29 (t, J=7.0 Hz, 3H).\",\"reactant_000\":\"CCOC(=O)N1C=Cc2c(oc3c(Cl)cc(Br)cc23)CC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9576390981674194,\"agent_000\":\"CC[SiH](CC)CC\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CCOC(=O)N1CCc2oc3c(Cl)cc(Br)cc3c2CC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([Cl:21])[C:5]2[O:20][C:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:13]=[CH:14][C:8]=3[C:6]=2[CH:7]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>>[Br:1][C:2]1[CH:3]=[C:4]([Cl:21])[C:5]2[O:20][C:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:14][C:8]=3[C:6]=2[CH:7]=1\",\"yield_000\":99.1},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.04490786790847778,\"rxn_id\":\"ord-24fd7b78aed445ca8d261f326e17388d\",\"index\":160670,\"rxn_smiles\":\"CO.NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1Cl.[Pt]>>NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1Cl\",\"procedure_details\":\"A solution of 50 mg (92 μmol) of the compound of Example 58 in 20 ml of methanol was hydrogenated in a continuous-flow hydrogenation apparatus fitted with a 5% Pt\\/C cartridge (H-Cube, from Thales Nano, Budapest, Model HC-2-SS) at a flow rate of 1 ml\\/min, a temperature of 60° C. and at standard pressure. After the reaction had ended, the solution was freed from the methanol on a rotary evaporator and the residue was purified by preparative HPLC [Method 23]. This gave 22 mg (44% of theory) of the title compound.\",\"reactant_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1Cl\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9550921320915222,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1Cl\",\"rxn_str\":\"[C:1](=[O:36])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12](\\/[CH:15]=[CH:16]\\/[C:17]([F:20])([F:19])[F:18])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]>CO.[Pt]>[C:1](=[O:36])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12]([CH2:15][CH2:16][C:17]([F:20])([F:18])[F:19])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.04712486267089844,\"rxn_id\":\"ord-9a361f33f4bc403e93ecdf340d1ca116\",\"index\":486536,\"rxn_smiles\":\"CO.NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F.[Pt]>>NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"procedure_details\":\"A solution of 30 mg (52 μmol) of the compound of Example 61 in 15 ml of methanol was hydrogenated in a continuous-flow hydrogenation apparatus fitted with a 5% Pt\\/C cartridge (H-Cube, from Thales Nano, Budapest, Model HC-2-SS) at a flow rate of 1 ml\\/min, a temperature of 60° C. and at standard pressure. After the reaction had ended, the solution was freed from the methanol on a rotary evaporator and the residue was purified by preparative HPLC [Method 23]. This gave 15 mg (50% of theory) of the title compound.\",\"reactant_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9528751373291016,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"rxn_str\":\"[C:1](=[O:39])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]([F:38])([F:37])[F:36])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12](\\/[CH:15]=[CH:16]\\/[C:17]([F:20])([F:19])[F:18])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]>CO.[Pt]>[C:1](=[O:39])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]([F:37])([F:36])[F:38])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12]([CH2:15][CH2:16][C:17]([F:20])([F:18])[F:19])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.04754018783569336,\"rxn_id\":\"ord-3d537ae618694a4088334381873e4a78\",\"index\":49571,\"rxn_smiles\":\"CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O.CO.[Pt]>>CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O\",\"procedure_details\":\"A solution of 25 mg (39 μmol) of the compound of Example 31 in 10 ml of methanol was hydrogenated in an H-Cube fitted with a platinum cartridge (5% Pt\\/C) (continuous-flow hydrogenation apparatus from Thales Nano, Budapest, Model HC-2-SS) at a flow rate of 1 ml\\/min, at 60° C. and under hydrogen at standard pressure. The resulting solution was freed from methanol on a rotary evaporator, and the residue was dissolved in 2 ml of acetonitrile and purified by preparative HPLC [Method 7]. This gave 8 mg (32% of theory) of the title compound.\",\"reactant_000\":\"CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9524598121643066,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12](\\/[CH:13]=[CH:14]\\/[C:15]([F:18])([F:17])[F:16])[C:11](=[O:19])[N:10]([CH2:20][C:21]([NH:23][CH:24]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]([F:43])([F:42])[F:41])[C:25]([NH:27][C:28]([CH3:33])([C:30]([NH2:32])=[O:31])[CH3:29])=[O:26])=[O:22])[N:9]=2)=[CH:4][CH:3]=1>CO.[Pt]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][CH2:14][C:15]([F:16])([F:17])[F:18])[C:11](=[O:19])[N:10]([CH2:20][C:21]([NH:23][CH:24]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]([F:41])([F:42])[F:43])[C:25]([NH:27][C:28]([CH3:29])([C:30]([NH2:32])=[O:31])[CH3:33])=[O:26])=[O:22])[N:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.047630906105041504,\"rxn_id\":\"ord-92af5e068d80441da34ed946421d393c\",\"index\":248059,\"rxn_smiles\":\"CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F.CO.[Pt]>>CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"procedure_details\":\"A solution of 168 mg (0.28 mmol) of the compound from Example 146 in 30 ml of methanol was hydrogenated by means of a continuous-flow hydrogenation apparatus (H-Cube, Thales Nano, Budapest, Model HC-2-SS), equipped with a 5% Pt\\/C catalyst cartridge, at 70° C. with a flow rate of 1 ml\\/min under standard pressure. The methanol was removed on a rotary evaporator and the residue was purified by preparative HPLC [Method 20]. This gave 96 mg (55% of theory) of the title compound.\",\"reactant_000\":\"CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9523690938949585,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"rxn_str\":\"[CH2:1]([NH:3][C:4](=[O:41])[O:5][CH2:6][CH:7]([NH:18][C:19](=[O:40])[CH2:20][N:21]1[C:25](=[O:26])[N:24](\\/[CH:27]=[CH:28]\\/[C:29]([F:32])([F:31])[F:30])[C:23]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=2)=[N:22]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([F:17])([F:16])[F:15])[CH3:2]>CO.[Pt]>[CH2:1]([NH:3][C:4](=[O:41])[O:5][CH2:6][CH:7]([NH:18][C:19](=[O:40])[CH2:20][N:21]1[C:25](=[O:26])[N:24]([CH2:27][CH2:28][C:29]([F:32])([F:31])[F:30])[C:23]([C:33]2[CH:34]=[CH:35][C:36]([Cl:39])=[CH:37][CH:38]=2)=[N:22]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([F:17])([F:16])[F:15])[CH3:2]\",\"yield_000\":null}]","literatureScore":0.96,"label":"LR ALL>>28","id":28},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.001256108283996582,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9987438917160034,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.002322077751159668,\"rxn_id\":\"ord-214ad747a1f341d8bd081a26de23f8fc\",\"index\":229462,\"rxn_smiles\":\"CC(=O)O.CCOC(C)=O.O=[N+]([O-])c1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Fe]>>Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"353 mg of iron dissolved in aqueous 5% acetic acid solution was activated at 100° C. 450 mg of [3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-[7 (3-morpholin-4-yl-propoxy)-6-nitro-quinazolin-4-yl]-amine (see, Journal of Medicinal Chemistry 2000, 43, 1380) dissolved in a mixture of ethylacetate and acetic acid (1:1) was added thereto dropwise, and refluxed. The hot reacted solution was filtered under a reduced pressure through celite pad, and the pad was washed with ethylacetate. The washed solvent was washed with saturated sodium bicarbonate solution several times. The organic layer was dried over magnesium sulfate, and filtered and distilled under a reduced pressure to obtain the title compound (353 mg, 83%).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976779222488403,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:31][CH2:32][CH2:33][CH2:34][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)=[C:25]([N+:28]([O-])=O)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1>C(O)(=O)C.C(OC(=O)C)C.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:31][CH2:32][CH2:33][CH2:34][N:35]4[CH2:36][CH2:37][O:38][CH2:39][CH2:40]4)=[C:25]([NH2:28])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1\",\"yield_000\":82.8},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0025284886360168457,\"rxn_id\":\"ord-5cc6890b875547de902e23ea2500d6fa\",\"index\":70006,\"rxn_smiles\":\"CCO.O=C([O-])O.O=[N+]([O-])c1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1.[Na+]>>Nc1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1\",\"procedure_details\":\"Stannous chloride dihydrate (478 mg; 2.13 mmol; 5 eq.) was added to a solution of Example 11 (200 mg; 0.43 mmol; 1 eq.) in EtOH (20 mL) and the resulting mixture was stirred at 70° C. for 3 hours, then at room temperature for 16 hours. The solution was diluted with sat. aq. NaHCO3 and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (c-hexane\\/ethyl acetate, 70\\/30) followed by crystallization from n-pentane afforded the title compound as an off-white solid.\",\"reactant_000\":\"O=[N+]([O-])c1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9974715113639832,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"Nc1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1\",\"rxn_str\":\"[F:1][C:2]1([F:33])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][C:26]([F:29])([F:28])[F:27])[N:15]=3)=[CH:10][C:9]=2[N+:30]([O-])=O)[CH2:3]1>CCO.C([O-])(O)=O.[Na+]>[F:33][C:2]1([F:1])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][C:26]([F:27])([F:28])[F:29])[N:15]=3)=[CH:10][C:9]=2[NH2:30])[CH2:3]1\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":\"O\",\"distance\":0.0025320053100585938,\"rxn_id\":\"ord-8be2ef3972144f088e5f0a9bf0a762e6\",\"index\":63590,\"rxn_smiles\":\"CO.O.O=[N+]([O-])c1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1.[Cl-].[Fe].[NH4+]>>Nc1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1\",\"procedure_details\":\"To a mixture of N-(3-(difluoromethoxy)phenyl)-6-nitro-2-(pyrazin-2-yl) quinazolin-4-amine (1.40 g, 3.4 mmol, 1.0 eq.) in MeOH-H2O (v\\/v, 3:1, 110 mL) was added NH4Cl (1.80 g, 34 mmol, 10.0 eq.) and Fe (1.91 g, 34 mmol, 10.0 eq.). The resulting mixture was stirred at 60° C. for 3 h. After the reaction was completed, the mixture was cooled to room temperature, and the iron was filtered off. The filtrate was concentrated to 15 ml, and a precipitate formed and was collected and dried in vacuo to give 1.13 g of N4-(3-(difluoromethoxy)phenyl)-2-(pyrazin-2-yl)quinazoline-4,6-diamine as a pale yellow solid (87.5%). LCMS m\\/z=381.1 (M+1) (Method B) (retention time=1.60 min), 1H-NMR (400 MHz, DMSO-d6): δ 9.69 (s, 1H), 9.52 (d, J=1.2 Hz, 1H), 8.75 (d, J=2.4 Hz, 1H), 8.69 (d, J=2.4 Hz, 1H), 8.30 (s, 1H), 7.87 (dd, J=8.4, 0.8 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.49-7.42 (m, 2H), 7.33-7.32 (m, 1H), 7.31 (t, J=7.4 Hz, 1H), 5.85 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9974679946899414,\"agent_000\":\"[Fe]\",\"agent_001\":\"[Cl-]\",\"agent_002\":\"[NH4+]\",\"temperature\":60.0,\"product_000\":\"Nc1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1\",\"rxn_str\":\"[F:1][CH:2]([F:30])[O:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([N+:21]([O-])=O)[CH:19]=3)[N:14]=[C:13]([C:24]3[CH:29]=[N:28][CH:27]=[CH:26][N:25]=3)[N:12]=2)[CH:7]=[CH:8][CH:9]=1.[NH4+].[Cl-]>CO.O.[Fe]>[F:30][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([NH2:21])[CH:19]=3)[N:14]=[C:13]([C:24]3[CH:29]=[N:28][CH:27]=[CH:26][N:25]=3)[N:12]=2)[CH:7]=[CH:8][CH:9]=1\",\"yield_000\":87.4},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0025365352630615234,\"rxn_id\":\"ord-ace4d398f5d9464ba65fd1e3f06cf8c1\",\"index\":464295,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1.[Cl-].[Fe].[NH4+]>>Nc1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1\",\"procedure_details\":\"N-(3-Bromo-5-nitrophenyl)-4-(trifluoromethyl)pyrimidin-2-amine (4.76 g, 13.11 mmol) was dissolved in ethanol (131 ml) and saturated solution of NH4Cl (1 mL) was added followed by Fe (3.66 g, 65.5 mmol). The reaction mixture was stirred at 80° C. for 30 minutes then cooled to room temperature. The solution was filtered through a short pad of silica gel and eluted with EtOAc. The phase were separated, the organics were dried, filtered, concentrated under reduced pressure to afford 5-bromo-N-[4-(trifluoromethyl)pyrimidin-2-yl]benzene-1,3-diamine as a beige powder.\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9974634647369385,\"agent_000\":\"[Fe]\",\"agent_001\":\"[Cl-]\",\"agent_002\":\"[NH4+]\",\"temperature\":80.0,\"product_000\":\"Nc1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:5]=[C:6]([N+:8]([O-])=O)[CH:7]=1.[NH4+].[Cl-]>C(O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[C:4]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:3]=1\",\"yield_000\":null}]","literatureScore":1,"label":"LR ALL>>225","id":225},"children":[{"depth":4,"reaction":{"scalabilityModelScore":5.9,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.03746253252029419,\"rxn_id\":\"ord-a89edf85823941f7a3b905c92d48ef2d\",\"index\":8545,\"rxn_smiles\":\"CCCCCCCCBr.CN(C)C=O.CO.O=C([O-])[O-].O=C1Nc2cc3c(cc2=C1c1ccc(Br)cc1)NC(=O)C=3c1ccc(Br)cc1.[K+].[K+]>>CCCCCCCCN1C(=O)C(c2ccc(Br)cc2)=c2cc3c(cc21)=C(c1ccc(Br)cc1)C(=O)N3CCCCCCCC\",\"procedure_details\":\"3,7-Bis-(4-bromo-phenyl)-1H,5H-pyrrolo[2,3-f]indole-2,6-dione (1.250 g, 2.519 mmol) (1.3) is dissolved into anhydrous dimethylformamide (50 cm3) and then potassium carbonate (3.482 g, 25.19 mmol) and 1-bromo-octane (1.1 cm3, 6.3 mmol) is added. The resulting mixture is heated to 90° C. for 21 hours before being cooled down, poured into methanol (500 cm3) and filtered to recover the pure product (1.320 g, Yield: 73%). NMR (1H, 300 MHz, CDCl3): δ 7.64 (d, J=8.7 Hz, 4H); 7.57 (d, J=8.7 Hz, 4H); 6.26 (s, 2H); 3.62 (t, J=7.1 Hz, 4H); 1.63 (m, 4H); 1.32 (m, 8H); 1.26 (m, 12H); 0.87 (t, J=6.8 Hz, 6H).\",\"reactant_000\":\"CCCCCCCCBr\",\"reactant_002\":\"CN(C)C=O\",\"reactant_001\":\"O=C1Nc2cc3c(cc2=C1c1ccc(Br)cc1)NC(=O)C=3c1ccc(Br)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9625374674797058,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"CCCCCCCCN1C(=O)C(c2ccc(Br)cc2)=c2cc3c(cc21)=C(c1ccc(Br)cc1)C(=O)N3CCCCCCCC\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2C(=O)NC3[C:19]=2[CH:18]=[C:17]2[C:13](=[C:14]([C:21]4[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=4)[C:15](=[O:20])[NH:16]2)[CH:12]=3)=[CH:4][CH:3]=1.[CH3:29][N:30]([CH3:33])[CH:31]=[O:32].C(=O)([O-])[O-].[K+].[K+].Br[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48]>CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:31](=[O:32])[N:30]([CH2:33][CH2:6][CH2:7][CH2:2][CH2:3][CH2:4][CH2:5][CH3:8])[C:29]3[C:19]=2[CH:18]=[C:17]2[C:13](=[C:14]([C:21]4[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=4)[C:15](=[O:20])[N:16]2[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH:12]=3)=[CH:4][CH:3]=1\",\"yield_000\":73.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.03879880905151367,\"rxn_id\":\"ord-1b4bb8a767e54f84ad42322c3324c0d0\",\"index\":696890,\"rxn_smiles\":\"CC(C)(C)OC(=O)NC1C(=O)Nc2ccccc2NC1=O.O=C(CBr)N1CCCC1>>CC(C)(C)OC(=O)NC1C(=O)N(CC(=O)N2CCCC2)c2ccccc2N(CC(=O)N2CCCC2)C1=O\",\"procedure_details\":\"Compound 14a is prepared in a manner similar to that used for preparation of Compound 14 h using previously prepared Compound 13 and pyrrolidinocarbonylmethyl bromide.\",\"reactant_000\":\"O=C(CBr)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OC(=O)NC1C(=O)Nc2ccccc2NC1=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9612011909484863,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OC(=O)NC1C(=O)N(CC(=O)N2CCCC2)c2ccccc2N(CC(=O)N2CCCC2)C1=O\",\"rxn_str\":\"[C:1]([O:5][C:6]([NH:8][CH:9]1[C:15](=[O:16])[NH:14][C:13]2[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=2[NH:11][C:10]1=[O:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:22]1([C:27]([CH2:29]Br)=[O:28])[CH2:26][CH2:25][CH2:24][CH2:23]1>>[N:22]1([C:27]([CH2:29][N:14]2[C:13]3[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=3[N:11]([CH2:29][C:27]([N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[O:28])[C:10](=[O:21])[CH:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:15]2=[O:16])=[O:28])[CH2:26][CH2:25][CH2:24][CH2:23]1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.04240995645523071,\"rxn_id\":\"ord-53a5c145d64c4b8ea004804828740818\",\"index\":715287,\"rxn_smiles\":\"CC(C)(C)OC(=O)CBr.CN(C)C=O.O=C1CCNC(=O)CCN1.[H-].[Na+]>>CC(C)(C)OC(=O)CN1CCC(=O)N(CC(=O)OC(C)(C)C)CCC1=O\",\"procedure_details\":\"3.3 g of perhydro-1,5-diazocine-2,6-dione are suspended in 30 ml of absolute DMF, and 732 mg of sodium hydride (80%) are then added. The mixture is stirred at RT for 15 min and then cooled to 0° C., and 3.76 ml of tert-butyl bromoacetate are then added. The mixture is stirred at 0° C. for 15 min and at RT for 30 min and then once more cooled to 0° C., and another 732 mg of sodium hydride (80%) are added. After 15 min, a further 3.76 ml of tert-butyl bromoacetate are added using a pipette, and after 15 min, the ice bath is removed and the mixture is stirred at RT overnight. The mixture is diluted with dichloromethane, water is added, the phases are separated and the organic phase is washed twice with water. The organic phase is dried over MgSO4 and concentrated, and the residue is dried under high vacuum and recrystallized from n-hexane. This gives 2.5 g of the title compound of melting point 180° C.; the mass spectrum shows the molecular peaks MH+ and MNH4+ at 371 and 388 Da, respectively.\",\"reactant_000\":\"O=C1CCNC(=O)CCN1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OC(=O)CBr\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9575900435447693,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CC(C)(C)OC(=O)CN1CCC(=O)N(CC(=O)OC(C)(C)C)CCC1=O\",\"rxn_str\":\"[NH:1]1[CH2:8][CH2:7][C:6](=[O:9])[NH:5][CH2:4][CH2:3][C:2]1=[O:10].[H-].[Na+].Br[CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]>CN(C=O)C>[C:18]([O:17][C:15]([CH2:14][N:1]1[C:2](=[O:10])[CH2:3][CH2:4][N:5]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:6](=[O:9])[CH2:7][CH2:8]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.04364597797393799,\"rxn_id\":\"ord-b30456e858fd4c948fa56e3aa53911d1\",\"index\":514020,\"rxn_smiles\":\"BrCc1ccccc1.CC(C)(C)OC(=O)CBr.CN(C)C=O.O=C([O-])[O-].O=S1(=O)NN=C(c2c[nH]c3ccccc23)c2ccccc21.[K+].[K+]>>O=C(O)Cn1cc(C2=NN(Cc3ccccc3)S(=O)(=O)c3ccccc32)c2ccccc21\",\"procedure_details\":\"The product of step c) (93 mg, 0.3 mmol) was dissolved in 3 mL DMF and treated with K2CO3 (50 mg, 0.36 mmol) and benzyl bromide (57 mg, 0.33 mmol). After stirring at 75° C. overnight, t-butyl bromoacetate (0.36 mmol, 70 mg) and was added along with an additional quantity of K2CO3 (0.39 mmol, 54 mg). The reaction was heated for an additional 2 hours. The crude reaction was partitioned between EtOAc and water. The organic layer was concentrated to dryness and treated with TFA (3 mL). After 1 h, the reaction was concentrated and purified by preparative LCMS to give the title compound. 1H NMR (DMSO-d6) δ 8.15 (d, 1H, J=3.6 Hz), 8.07-7.94 (m, 3H), 7.92 (s, 1H), 7.59 (d, J=7.5 Hz, 1H), 7.51-7.31 (m, 6H), 7.22 (t, J=7.2 Hz, 1H), 7.04 (t, J=7.8 Hz, 1H), 5.12 (s, 2H), 5.07 (s, 2H); MS: ESI (negative): 444 (M−H).\",\"reactant_000\":\"O=S1(=O)NN=C(c2c[nH]c3ccccc23)c2ccccc21\",\"reactant_002\":\"BrCc1ccccc1\",\"reactant_001\":\"CC(C)(C)OC(=O)CBr\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.956354022026062,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":75.0,\"product_000\":\"O=C(O)Cn1cc(C2=NN(Cc3ccccc3)S(=O)(=O)c3ccccc32)c2ccccc21\",\"rxn_str\":\"[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[S:13](=[O:21])(=[O:20])[NH:12][N:11]=2)=[CH:2]1.C([O-])([O-])=O.[K+].[K+].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.Br[CH2:37][C:38]([O:40]C(C)(C)C)=[O:39]>CN(C=O)C>[CH2:28]([N:12]1[N:11]=[C:10]([C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[N:1]([CH2:37][C:38]([OH:40])=[O:39])[CH:2]=2)[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[S:13]1(=[O:21])=[O:20])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.04575759172439575,\"rxn_id\":\"ord-b8ac393b893c42cfb6d34015ef8c6939\",\"index\":430960,\"rxn_smiles\":\"CN(C)C=O.N#Cc1ccc(CBr)cc1.O.O=C1NCCN1.[H-].[Na+]>>N#Cc1ccc(CN2CCN(Cc3ccc(C#N)cc3)C2=O)cc1\",\"procedure_details\":\"To sodium hydride (2.4 g, 60 mmol) in dimethylformamide (50 mL) at 0° C. was added imidazolin-2-one (2.6 g, 30 mmol). After stirring for 20 minutes 4-(bromomethyl)benzonitrile (13 g, 66 mmol) was added and the mixture was warmed to ambient temperature. After stirring for 1 hour the reaction was poured into water and a solid formed. The solid was filtered to give 4,4'-[(2-oxoimidazolin-1,3-diyl)bis(methylene)]-bis(benzonitrile). NMR (CDCl3) 7.65 (d,4), 7.4 (d,4), 4.45 (s,4), 3.2 (s,4) ppm.\",\"reactant_000\":\"O=C1NCCN1\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(CBr)cc1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9542424082756042,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"N#Cc1ccc(CN2CCN(Cc3ccc(C#N)cc3)C2=O)cc1\",\"rxn_str\":\"[H-].[Na+].[NH:3]1[CH2:7][CH2:6][NH:5][C:4]1=[O:8].Br[CH2:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1.O>CN(C)C=O>[O:8]=[C:4]1[N:5]([CH2:10][C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)[CH2:6][CH2:7][N:3]1[CH2:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1\",\"yield_000\":null}]","literatureScore":0.96,"label":"T5 AT ER UA TTL ALL>>732","id":732},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005201458930969238,\"rxn_id\":\"ord-d187d104e8734ea4b08de971ecaec265\",\"index\":768853,\"rxn_smiles\":\"BrCCCBr.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1O>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCBr\",\"procedure_details\":\"The title compound was prepared from 1,3-dibromopropane and 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one (Example 29) following the procedure outlined in Example 25. 1H NMR (400 MHz, DMSO-d6): δ 9.53 (s, 1H), 8.81 (s, 2H), 7.96 (d, 1H), 7.22 (d, 1H), 4.65 (s, 1H), 4.11 (t, 2H), 3.93 (s, 3H), 3.77 (t, 2H), 2.18 (m, 2H); MS (ESI): 472.7.\",\"reactant_000\":\"BrCCCBr\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947985410690308,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCBr\",\"rxn_str\":\"[Br:1][CH2:2][CH2:3][CH2:4]Br.[Cl:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([Cl:28])[C:12]=1[NH:13][C:14]1[C:23]2[C:18](=[C:19]([OH:26])[C:20]([O:24][CH3:25])=[CH:21][CH:22]=2)[O:17][C:16](=[O:27])[CH:15]=1>>[Br:1][CH2:2][CH2:3][CH2:4][O:26][C:19]1[C:20]([O:24][CH3:25])=[CH:21][CH:22]=[C:23]2[C:18]=1[O:17][C:16](=[O:27])[CH:15]=[C:14]2[NH:13][C:12]1[C:11]([Cl:28])=[CH:10][N:9]=[CH:8][C:7]=1[Cl:6]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008294224739074707,\"rxn_id\":\"ord-b95b566c4ed343a68f9d559faf3a765e\",\"index\":103644,\"rxn_smiles\":\"BrCCCBr.N#Cc1cc2c(Oc3ccc(NC(=O)NC4CC4)c(Cl)c3)ccnc2cc1O>>N#Cc1cc2c(Oc3ccc(NC(=O)NC4CC4)c(Cl)c3)ccnc2cc1OCCCBr\",\"procedure_details\":\"The title compound (129 mg, 0.250 mmol, 15.6%) was obtained as light brown crystals from an N-(4-(6-cyano-7-hydroxy-4-quinolyl)oxy-2-chlorophenyl)-N\\u2032-cyclopropylurea crude product (500 mg, 1.60 mmol) and 1,3-dibromopropane, by the same procedure as in Example 7.\",\"reactant_000\":\"BrCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1cc2c(Oc3ccc(NC(=O)NC4CC4)c(Cl)c3)ccnc2cc1O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917057752609253,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc2c(Oc3ccc(NC(=O)NC4CC4)c(Cl)c3)ccnc2cc1OCCCBr\",\"rxn_str\":\"[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[OH:13])[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][CH:25]2[CH2:27][CH2:26]2)=[O:23])=[C:17]([Cl:28])[CH:16]=1)#[N:2].[Br:29][CH2:30][CH2:31][CH2:32]Br>>[Br:29][CH2:30][CH2:31][CH2:32][O:13][C:12]1[CH:11]=[C:10]2[C:5]([C:6]([O:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][CH:25]4[CH2:26][CH2:27]4)=[O:23])=[C:17]([Cl:28])[CH:16]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[C:1]#[N:2]\",\"yield_000\":15.6},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.009001731872558594,\"rxn_id\":\"ord-fb000c2447784f589143e866bd9835aa\",\"index\":217587,\"rxn_smiles\":\"BrCCCBr.CN(C)C=O.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.O=C([O-])[O-].[K+].[K+]>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCBr\",\"procedure_details\":\"To a solution of 7-hydroxy-4-(1H-indol-5-yloxy)-6-methoxyquinazoline (1 g, 3.2 mmol), (prepared as described for the starting material in Example 107), in DMF (50 ml) was added powdered potassium carbonate (1.32 g, 9.6 mmol) and 1,3-dibromopropane (6.43 g, 32 mmol). The reaction was heated at 50° C. for 2 hours. The inorganic material was filtered off and then the DMF removed. The residue was partitioned between methylene chloride\\/water. The organics were separated, dried over MgSO4, filtered, evaporated in vacuo and purified by flash chromatography eluting from methylene chloride to 5% methanol\\/95% methylene chloride. The product was concentrated in vacuo, triturated with ether and the resulting solid filtered to give 7-(3-bromopropoxy)-4-(1H-indol-5-yloxy)-6-methoxyquinazoline (900 mg, 66%) as a white solid.\",\"reactant_000\":\"COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9909982681274414,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCBr\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][CH:17]=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:22][CH3:23].C(=O)([O-])[O-].[K+].[K+].[Br:30][CH2:31][CH2:32][CH2:33]Br>CN(C=O)C>[Br:30][CH2:31][CH2:32][CH2:33][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][CH:17]=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:22][CH3:23]\",\"yield_000\":65.7},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010468721389770508,\"rxn_id\":\"ord-9e4c5c0c16ca4e189c38b8478945bf50\",\"index\":5134,\"rxn_smiles\":\"BrCCCCBr.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1O>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCCBr\",\"procedure_details\":\"8-(4-Bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one was prepared from 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxyquinolin-2(1H)-one (Example 11, Step 1) and 1,4-dibromobutane following the procedure outlined in Example 11, Step 2. MS (ESI): 485.8.\",\"reactant_000\":\"BrCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9895312786102295,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCCBr\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:23])[C:7]=1[NH:8][C:9]1[C:18]2[C:13](=[C:14]([OH:21])[C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[NH:12][C:11](=[O:22])[CH:10]=1.[Br:24][CH2:25][CH2:26][CH2:27][CH2:28]Br>>[Br:24][CH2:25][CH2:26][CH2:27][CH2:28][O:21][C:14]1[C:15]([O:19][CH3:20])=[CH:16][CH:17]=[C:18]2[C:13]=1[NH:12][C:11](=[O:22])[CH:10]=[C:9]2[NH:8][C:7]1[C:6]([Cl:23])=[CH:5][N:4]=[CH:3][C:2]=1[Cl:1]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010738372802734375,\"rxn_id\":\"ord-f89c952ec92f4e0f9eb9016a13fd0c48\",\"index\":635986,\"rxn_smiles\":\"BrCCCBr.Oc1cc(F)cc(F)c1>>Fc1cc(F)cc(OCCCBr)c1\",\"procedure_details\":\"Analogously to Example 91b, 0.98 g of 3,5-difluorophenol and 15.2 g of 1,3-dibromopropane are reacted. The title compound is obtained as a colourless oil. Rf=0.70 (1:6 EtOAc-heptane); Rt=5.13.\",\"reactant_000\":\"Oc1cc(F)cc(F)c1\",\"reactant_002\":null,\"reactant_001\":\"BrCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9892616271972656,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1cc(F)cc(OCCCBr)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([F:8])[CH:7]=1.[Br:10][CH2:11][CH2:12][CH2:13]Br>>[Br:10][CH2:11][CH2:12][CH2:13][O:9][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"AT UA ER ALL>>530","id":530},"children":[{"depth":6,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.004299342632293701,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9957006573677063,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.004652976989746094,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9953470230102539,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00585097074508667,\"rxn_id\":\"ord-51bfffc1cc3f48bfba7729fb1fa37a5a\",\"index\":347091,\"rxn_smiles\":\"BrBr.COC(=O)c1sc(-c2ccccc2)cc1O>>COC(=O)c1sc(-c2ccccc2)c(Br)c1O\",\"procedure_details\":\"Prepared by the method described in Example 4 from methyl 3-hydroxy-5-phenyl-2-thiophenecarboxylate (5.0 g, 21 mmoles) and bromine (3.4 g, 21 mmoles). Recrystallization from methanol gave the product (4.0 g); mp 85°-87° C.\",\"reactant_000\":\"COC(=O)c1sc(-c2ccccc2)cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941490292549133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)c1sc(-c2ccccc2)c(Br)c1O\",\"rxn_str\":\"[OH:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14].[Br:17]Br>>[OH:1][C:2]1[C:6]([Br:17])=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14]\",\"yield_000\":60.8},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.006023406982421875,\"rxn_id\":\"ord-cec279efa24d480ba329f30936792dee\",\"index\":224777,\"rxn_smiles\":\"BrBr.CC(=O)O.O=C(O)c1cc2ccccc2cc1O>>O=C(O)c1cc2ccccc2c(Br)c1O\",\"procedure_details\":\"3-Hydroxynaphthalene-2-carboxylic acid (3.0 g, 15.9 mmol) was suspended in acetic acid (40 mL) and with vigorous stirring a solution of bromine (817 μL, 15.9 mmol) in acetic acid (10 mL) was added drop wise during 30 minutes. The suspension was stirred at room temperature for 1 hour, filtered and washed with water. Drying in vacuo afforded 3.74 g (88%) of 4-bromo-3-hydroxynaphthalene-2-carboxylic acid as a solid.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"O=C(O)c1cc2ccccc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9939765930175781,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C(O)c1cc2ccccc2c(Br)c1O\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([C:12]([OH:14])=[O:13])=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[Br:15]Br>C(O)(=O)C>[Br:15][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:12]([OH:14])=[O:13])[C:2]=1[OH:1]\",\"yield_000\":88.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.006250619888305664,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9937493801116943,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null}]","literatureScore":1,"label":"UA T5 AT ER TTL ALL>>527","id":527},"children":[{"depth":7,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":8,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":9,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":217}]},{"depth":9,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":217}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":217}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":8,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":217}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.58,"id":154,"pathId":217}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":7,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.58,"id":522,"pathId":217}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RRIGCTITGHGCKU","smiles":"OC1=C(Br)C2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.8,"id":527,"pathId":217}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[Br:24]Br>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([c:21]([c:7]3[n:8][cH:9][n:10]2)[Br:24])[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];10.1.1;Bromination"},{"depth":6,"reaction":{"label":"UA T5 AT ER TTL ALL>>86","id":86},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"VEFLKXRACNJHOV","smiles":"BrCCCBr","intrinsicScore":0.8,"id":86,"pathId":217}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YDHQHLUEUGDPNP","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCBr","intrinsicScore":0.55,"id":530,"pathId":217}],"RXN":"[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[OH:24])[N+:18](=[O:19])[O-:20])[Cl:10])[F:9].[CH2:26]([CH2:25][Br:28])[CH2:27]Br>>[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[O:24][CH2:27][CH2:26][CH2:25][Br:28])[N+:18](=[O:19])[O-:20])[Cl:10])[F:9];1.7.9;Williamson"},{"depth":5,"reaction":{"label":"AT UA ER ALL>>925","id":925},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEEGQDGJIXWFIQ","smiles":"C1COC=CN1","intrinsicScore":0.55,"id":925,"pathId":217}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"LAGYVWYIGZOTJU","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOC=C1","intrinsicScore":0.75,"id":732,"pathId":217}],"RXN":"c1cc(c(cc1Nc2c3cc(c(c(c3ncn2)Br)OCCCBr)[N+](=O)[O-])Cl)F.C1COC=CN1>>c1cc(c(cc1Nc2c3cc(c(c(c3ncn2)Br)OCCCN4CCOC#C4)[N+](=O)[O-])Cl)F;0.0;Unrecognized"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HIYCMFOTUDUXKH","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOC=C1","intrinsicScore":0.051,"id":225,"pathId":217}],"RXN":"[cH:25]1[cH:26][c:27]([c:28]([cH:29][c:24]1[NH:23][c:2]2[c:1]3[cH:11][c:9]([c:8]([c:7]([c:6]3[n:5][cH:4][n:3]2)[Br:22])[O:12][CH2:13][CH2:14][CH2:15][N:16]4[CH2:21][CH2:20][O:19][CH:18]=[CH:17]4)[N+:10](=O)[O-])[Cl:30])[F:31]>CCO.Cl.[Fe]>[cH:25]1[cH:26][c:27]([c:28]([cH:29][c:24]1[NH:23][c:2]2[c:1]3[cH:11][c:9]([c:8]([c:7]([c:6]3[n:5][cH:4][n:3]2)[Br:22])[O:12][CH2:13][CH2:14][CH2:15][N:16]4[CH2:21][CH2:20][O:19][CH:18]=[CH:17]4)[NH2:10])[Cl:30])[F:31];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":217}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:21]([c:19]([c:18]3[n:17][cH:16][n:15]2)[Br:20])[O:22][CH2:23][CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][O:29][CH:28]=[CH:27]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:21]([c:19]([c:18]3[n:17][cH:16][n:15]2)[Br:20])[O:22][CH2:23][CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)[NH2:1])[Cl:13])[F:11];7.6.1;Alkene"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":217}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":217}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":217}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.518","depth":0,"reaction":{"label":">>0","id":0,"pathId":224},"children":[{"depth":1,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002493739128112793,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975062608718872,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.00285494327545166,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971450567245483,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.002886652946472168,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971133470535278,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003403782844543457,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9965962171554565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003649115562438965,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.996350884437561,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"LR ALL>>28","id":28},"children":[{"depth":3,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006411254405975342,\"rxn_id\":\"ord-73de563950e54f3a8a473ab1f9c7e3c2\",\"index\":86652,\"rxn_smiles\":\"CN(C)C=O.O.O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12.OCC1CC1.[H-].[Na+]>>O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"procedure_details\":\"Cyclopropylmethyl alcohol (0.921 ml, 11.4 mmol) was added to a stirring suspension of NaH (455 mg, 11.4 mmol) in DMF (20 ml) under an argon atmosphere. The resulting solution was allowed to stir at RT for 20 min. 6-chloro-7-fluoro-8-nitro-9H-β-carboline (500 mg, 1.9 mmol) was added to the stirring solution and the resulting mixture was allowed to stir at RT. Upon addition of H2O, a brown solid precipitated out which was filtered to give the desired 6-chloro-7-cyclopropylmethyoxy-8-nitro-9H-β-carboline (510 mg, 85%). 1H-NMR (300 MHz, DMSO-d6): δ 0.35 (m, 2H), 0.59 (m, 2H), 1.32 (m, 1H), 4.04 (d, 2H), 8.21 (d, 1H), 8.46 (d, 1H), 8.90 (s, 1H), 9.02 (s, 1H), 12.32 (b, 1H). Retention Time (LC, method: ammonium acetate standard): 2.63 min. MS (M+H+): 318.\",\"reactant_000\":\"O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12\",\"reactant_002\":null,\"reactant_001\":\"OCC1CC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9935887455940247,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1F)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1[O:5][CH2:4][CH:1]1[CH2:3][CH2:2]1)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1\",\"yield_000\":84.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006817042827606201,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9931829571723938,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.007981956005096436,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9920180439949036,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00798940658569336,\"rxn_id\":\"ord-e13729e09b02453d8b2ae8502f41e869\",\"index\":593117,\"rxn_smiles\":\"CC(C)(C)[O-].CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-].OCC(F)F.[K+]>>CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"procedure_details\":\"The subtitle compound is prepared from N-(4-bromophenyl)-2-fluoro-4-methylamino-5-nitro-benzamide, 2,2-difluoroethanol and KOtBu in analogy to example 1e.\",\"reactant_000\":\"CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9920105934143066,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2F)=[CH:4][CH:3]=1.[F:23][CH:24]([F:27])[CH2:25][OH:26].CC([O-])(C)C.[K+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2[O:26][CH2:25][CH:24]([F:27])[F:23])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008773088455200195,\"rxn_id\":\"ord-c07b2acbc69f47289d653f004b6d071c\",\"index\":64408,\"rxn_smiles\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12.Cl.OCC(F)F.[H-].[Na+]>>COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"procedure_details\":\"Sodium hydride (1.21 g, 30 mmol, as a 60% suspension in mineral oil) was charged into a round bottom flask equipped with magnetic stirring and a nitrogen blanket, washed twice with 10 mL hexanes, dried of residual hexanes under a nitrogen stream, and suspended in 1,2-dimethoxyethane (20 mL). After cooling in an ice bath to about 10° C., 2-fluoro-6-trifluoromethyl-N-(5, 8-di-methoxy[ 1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide (4.21 g, about 98.5% purity, 10 mmol) was added over about 5 min, rinsing in with 1 mL 1,2-dimethoxyethane. A slight exotherm to about 13° C. occurred. Continued ice bath cooling lowered temperature to about 6° C. over about 10 min. To the off-white suspension was added 2,2-difluoroethanol (0.815 niL, 13 mmol) over about 5 min. A slight exotherm to about 13° C. occurred. The light tan suspension was stirred at about 5-10° C. for about 1 hr, then the ice bath was removed. The temperature peaked at about 28° C. (about 2° C. above room temperature) about 0.5 hr later. The tan suspension was stirred overnight (about 20 hr total reaction time), then worked up by addition of the reaction mixture over about 7 min into 5% hydrochloric acid (80 mL, 112 mmol) at about 5-10° C. with ice bath cooling. The suspension was stirred about 18 min at about 9° C., then filtered, washed twice with 15 mL water each, washed twice with 15 mL methanol each, air-dried for about 2 hr, and finally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide to afford the product as a white powder (4.34 g, about 92.8% purity, 8.3 mmol, about 83% yield).\",\"reactant_000\":\"OCC(F)F\",\"reactant_002\":null,\"reactant_001\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9912269115447998,\"agent_000\":\"Cl\",\"agent_001\":\"[H-]\",\"agent_002\":\"[Na+]\",\"temperature\":10.0,\"product_000\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"rxn_str\":\"[H-].[Na+].F[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15].[F:31][CH:32]([F:35])[CH2:33][OH:34].Cl>>[F:31][CH:32]([F:35])[CH2:33][O:34][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:11])([F:12])[F:13])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15]\",\"yield_000\":83.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>228","id":228},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.0052683353424072266,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9947316646575928,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005525708198547363,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944742918014526,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.005835771560668945,\"rxn_id\":\"ord-6569ee74ee084f45aee0cc6bab387a3a\",\"index\":556261,\"rxn_smiles\":\"BrBr.CC(=O)O.Nc1ccc2nc(C(F)(F)F)[nH]c2c1>>Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"procedure_details\":\"To a solution of 3.2 g (16 mmol) of 2-trifluoromethyl-5-aminobenzimidazole in 50 ml of AcOH was added 0.34 ml (6.6 mmol) of Br2 dropwise and resulting reaction mixture was stirred for 1 h at 25° C. The reaction mixture was concentrated in vacuo and purified on silica gel column chromatography (10% MeOH\\/CHCl3) to yield 1.7 g (6.2 mmol, 94%) of the desired product.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.994164228439331,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"rxn_str\":\"[F:1][C:2]([F:14])([F:13])[C:3]1[NH:4][C:5]2[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[Br:15]Br>CC(O)=O>[F:14][C:2]([F:1])([F:13])[C:3]1[NH:4][C:5]2[C:11]([Br:15])=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1\",\"yield_000\":93.9},{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.005841076374053955,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994158923625946,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005856215953826904,\"rxn_id\":\"ord-1d443c1852a24a44bc10d8df0c32bd94\",\"index\":784164,\"rxn_smiles\":\"BrBr.ClC(Cl)Cl.Nc1ccc2ncsc2c1>>Nc1ccc2ncsc2c1Br\",\"procedure_details\":\"To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67 mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27 mmol) in CHCl3 (10 ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5:1) to give 7-bromobenzo[d]thiazol-6-amine (80 mg, 80%).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncsc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941437840461731,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ncsc2c1Br\",\"rxn_str\":\"[S:1]1[C:5]2[CH:6]=[C:7]([NH2:10])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Br:11]Br>C(Cl)(Cl)Cl>[Br:11][C:6]1[C:5]2[S:1][CH:2]=[N:3][C:4]=2[CH:9]=[CH:8][C:7]=1[NH2:10]\",\"yield_000\":129.3}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>528","id":528},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":224}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":224}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":224}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":224}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.3,"id":159,"pathId":224}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.3,"id":522,"pathId":224}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CUHXEXBIVQEVJM","smiles":"[O-][N+](=O)C1=CC2=C(N=CN=C2NC2=CC(Cl)=C(F)C=C2)C(Br)=C1F","intrinsicScore":0.33,"id":528,"pathId":224}],"RXN":"[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([cH:11][c:3]3[n:2][cH:1][n:23]2)[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22].[Br:24]Br>>[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([c:11]([c:3]3[n:2][cH:1][n:23]2)[Br:24])[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22];10.1.1;Bromination"},{"depth":4,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.33,"id":43,"pathId":224}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"JWFJQOCJPWGBQR","smiles":"[O-][N+](=O)C1=C(OCCCN2CCOCC2)C(Br)=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1","intrinsicScore":0.71,"id":228,"pathId":224}],"RXN":"[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])F)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9].[CH2:29]1[CH2:30][O:31][CH2:32][CH2:33][N:28]1[CH2:27][CH2:26][CH2:25][OH:24]>>[cH:8]1[cH:7][c:6]([c:5]([cH:4][c:3]1[NH:2][c:1]2[c:15]3[cH:16][c:17]([c:21]([c:22]([c:14]3[n:13][cH:12][n:11]2)[Br:23])[O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)[N+:18](=[O:19])[O-:20])[Cl:10])[F:9];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":224}],"RXN":"[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[N+:31](=O)[O-])[Cl:26])[F:30]>>[cH:29]1[cH:28][c:27]([c:25]([cH:24][c:23]1[NH:22][c:21]2[c:14]3[cH:13][c:12]([c:11]([c:16]([c:15]3[n:18][cH:19][n:20]2)[Br:17])[O:10][CH2:9][CH2:8][CH2:7][N:5]4[CH2:4][CH2:3][O:2][CH2:1][CH2:6]4)[NH2:31])[Cl:26])[F:30];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":224}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":224}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":224}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.526","depth":0,"reaction":{"label":">>0","id":0,"pathId":728},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":728}]},{"depth":7,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":728}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":728}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":728}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":728}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":728}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":728}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":728}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":728}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":728}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":728}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":728}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":728}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.533","depth":0,"reaction":{"label":">>0","id":0,"pathId":163},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.6,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.008023500442504883,\"rxn_id\":\"ord-42dc5bd007e148f297483fd574a84112\",\"index\":514864,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCN(CC)CC.Cl.Cl.N#Cc1ccc(Cn2cncc2CCN)cc1F>>N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride (0.92 g, 0.0029 mmol) in acetonitrile (150 mL) and triethylamine (3.2 mL) was added 2-bromoethyl ether (0.839 mL, 0.0067 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in uacuo and the residue was dissolved in EtOAc which was washed twice with 1M HCl (100 mL). The HCl layers were combined and adjusted to pH=9 with solid Na2CO3 and extraxcted 3 times with EtOAc. The EtOAc layers were combined and dried with brine and MgSO4. Removal of the EtOAc in vacuo yielded the title compound which was used as is in the next step.\",\"reactant_000\":\"N#Cc1ccc(Cn2cncc2CCN)cc1F\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919764995574951,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=2)[CH:9]=[N:8][CH:7]=1.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>C(#N)C.C(N(CC)CC)C>[F:20][C:14]1[CH:13]=[C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][N:3]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:7][N:8]=[CH:9]2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.008291244506835938,\"rxn_id\":\"ord-08bb54aa0ab244ff90317c31f9d4c5e8\",\"index\":731783,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.NC1CCN(Cc2ccccc2)CC1.O=C([O-])[O-].[K+].[K+]>>c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"procedure_details\":\"To a stirred mixture of 4-amino-1-benzylpiperidine (1.53 mL, 7.5 mmol), K2CO3 (2.28 g, 16.5 mmol) and DMF (15 mL) heated at 50° C. was added dropwise over 60 min bis(2-bromoethyl) ether (0.96 mL, 7.65 mmol). After stirring for 6 hours at 80° C., the solvent was removed by blowing with a stream of nitrogen over 2 hours. The residue was purified on a silica gel column to give 1.7 g (87%) of 4-(1-benzyl-piperidin-4-yl)morpholine as a waxy solid.\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"NC1CCN(Cc2ccccc2)CC1\",\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9917087554931641,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"rxn_str\":\"[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>CN(C=O)C>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:1]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1\",\"yield_000\":87.1},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.008305191993713379,\"rxn_id\":\"ord-ac7a693c46694fd5b13039f5c104d79e\",\"index\":134482,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N.O=C([O-])[O-].[K+].[K+]>>CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"procedure_details\":\"cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane\\/methanol\\/ammonia 100:0:0->140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m\\/e=403.3 [(M+H)+].\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9916948080062866,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"rxn_str\":\"[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]\",\"yield_000\":68.6},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.00859677791595459,\"rxn_id\":\"ord-aa3eb88c8e6c445794e16d41429514f0\",\"index\":719114,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O.CCN(CC)CC.Cl.Cl>>CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-2-methyl-imidazol-1-ylmethyl]-2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile dihydrochloride (as described in Example 11) (0.25 g, 0.456 mmol) in acetonitrile (35.0 mL) and triethylamine (1.8 mL) was added 2-bromoethyl ether (0.133 mL, 1.06 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in vacuo to obtain the title compound after purification by preparative HPLC.\",\"reactant_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9914032220840454,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]4([CH2:36][CH3:37])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]4=[O:35])[CH:22]=3)[CH:13]=2)[C:9]([CH3:38])=[N:8][CH:7]=1.Br[CH2:40][CH2:41][O:42][CH2:43][CH2:44]Br>C(#N)C.C(N(CC)CC)C>[CH2:36]([C:27]1([C:23]2[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=2)[O:20][C:14]2[CH:13]=[C:12]([CH2:11][N:10]3[C:6]([CH2:5][CH2:4][N:3]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[CH:7][N:8]=[C:9]3[CH3:38])[CH:19]=[CH:18][C:15]=2[C:16]#[N:17])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]1=[O:35])[CH3:37]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.008690357208251953,\"rxn_id\":\"ord-90e436a959164d40ab8c094946564425\",\"index\":740936,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.Nc1ccc(Br)c(Cl)c1.O.O=C([O-])[O-].[I-].[K+].[K+].[K+]>>Clc1cc(N2CCOCC2)ccc1Br\",\"procedure_details\":\"4-Bromo-3-chloroaniline (500 mg) was dissolved in DMF (10 ml), and bis(2-bromoethyl)ether (1.12 g), K2CO3 (1.34 g), and potassium iodide (80 mg) were added thereto, followed by stirring at 80° C. for 2 days. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 20% EtOAc\\/hexane) to obtain 4-(4-bromo-3-chlorophenyl)morpholine (263 mg).\",\"reactant_000\":\"Nc1ccc(Br)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":48.0,\"reactant_003\":null,\"similarity\":0.991309642791748,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[I-]\",\"agent_002\":\"[K+]\",\"temperature\":80.0,\"product_000\":\"Clc1cc(N2CCOCC2)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:9].Br[CH2:11][CH2:12][O:13][CH2:14][CH2:15]Br.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][C:3]=1[Cl:9]\",\"yield_000\":39.3}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":\"CCO\",\"distance\":0.0034121274948120117,\"rxn_id\":\"ord-c978110d0ebb47c5ab077decdb013eb8\",\"index\":750238,\"rxn_smiles\":\"CCO.CP(C)C.[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1.[NH4+].[OH-].c1ccncc1>>NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"procedure_details\":\"To a solution of (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 0.230 mmol) in pyridine (2 mL) was added NH4OH (200 μl) and trimethylphosphine (344 μl, 0.344 mmol) sequentially at room temperature. The reaction mixture was stirred for 2 h. After EtOH (1 mL) was added, the reaction mixture was concentrated in vacuo. The crude product was purified by flash chromatography (20% MeOH in DCM containing 0.5% NH3\\/DCM) to provide 89.6 mg of (S)\\u2014N-(2-amino-1-(3-chloro-5-fluorophenyl)ethyl)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamide (79%). LCMS (m\\/z): 488.2 (MH+), 0.66 min. 1H NMR (500 MHz, METHANOL-d4) δ ppm 7.98-7.89 (m, 1H), 7.89-7.79 (m, 1H), 7.74 (td, J=1.4, 8.0 Hz, 1H), 7.69-7.61 (m, 1H), 7.41-7.28 (m, 1H), 7.27-7.08 (m, 2H), 5.27-5.12 (m, 1H), 4.07 (dd, J=3.8, 11.0 Hz, 2H), 3.69-3.52 (m, 2H), 3.14-3.03 (m, 2H), 2.96 (tt, J=3.9, 11.7 Hz, 1H), 2.02-1.77 (m, 4H).\",\"reactant_000\":\"[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996587872505188,\"agent_000\":\"CP(C)C\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]([C:14]2[CH:35]=[CH:34][C:17]([C:18]([NH:20][C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=3)[CH2:22][N:23]=[N+]=[N-])=[O:19])=[C:16]([F:36])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[NH4+].[OH-].CP(C)C.CCO>N1C=CC=CC=1>[NH2:23][CH2:22][C@@H:21]([NH:20][C:18](=[O:19])[C:17]1[CH:34]=[CH:35][C:14]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([CH:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:4]=2)=[CH:15][C:16]=1[F:36])[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=1\",\"yield_000\":79.8},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004088282585144043,\"rxn_id\":\"ord-042249e7216a47579d0f62148c807cd2\",\"index\":714256,\"rxn_smiles\":\"C1CCOC1.C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21>>NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"procedure_details\":\"20 μL of a 1M trimethylphosphine\\/tetrahydrofuran solution was added to 6 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-azidoethyl) ester dissolved in a mixture of 0.15 mL of tetrahydrofuran and 0.02 mL of water at room temperature, and the mixture was stirred for 13 hours. After the solvent was distilled under reduced pressure, the residue was purified by reverse phase column chromatography (Wako gel 50C18 (made by Wako Pure Chemical Industries Ltd.), eluent: water to a 50% aqueous solution of acetonitrile), and the obtained solids were further washed with tetrahydrofuran, thereby yielding 2 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-aminoethyl)ester.\",\"reactant_000\":\"[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":13.0,\"reactant_003\":null,\"similarity\":0.995911717414856,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"rxn_str\":\"CP(C)C.O1CCCC1.[N:10]([CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17])=[N+]=[N-]>O1CCCC1.O>[NH2:10][CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17]\",\"yield_000\":35.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0043354034423828125,\"rxn_id\":\"ord-d978c1c7e23041a1b604dc1dd6ff7a6f\",\"index\":562746,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1>>NCc1cncc(C#Cc2ccccc2)c1\",\"procedure_details\":\"To a solution of 3-(azidomethyl)-5-(phenylethynyl)pyridine (7.8 g, 33.3 mmol) in tetrahydrofuran (101 mL) at 0° C. was added trimethylphosphine (1M in tetrahydrofuran, 49.9 mL, 49.9 mmol). After evolution of nitrogen had slowed, the ice bath was removed and stirring continued for 1 h. To this was added water (6.0 mL, 333 mmol) and the mixture stirred at room temperature for 2 h. The reaction was concentrated, dissolved in ether, washed with water (5×), then brine, dried over potassium carbonate, filtered, and concentrated to give 5.96 g (77%) as a faint yellow solid which was used without purification. 1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H)1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H). 13C NMR (CDCl3) δ: 150.8, 147.9, 137.8, 137.4, 131.8, 128.9, 128.6, 122.7, 120.3, 92.7, 86.1, 43.7. Mass spec.: 209.1 (MH)+.\",\"reactant_000\":\"[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9956645965576172,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCc1cncc(C#Cc2ccccc2)c1\",\"rxn_str\":\"[N:1]([CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[N+]=[N-].CP(C)C.O>O1CCCC1>[C:13]1([C:12]#[C:11][C:9]2[CH:10]=[C:5]([CH2:4][NH2:1])[CH:6]=[N:7][CH:8]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.005223870277404785,\"rxn_id\":\"ord-089f68b08fe543bfbdedd8c9521524ae\",\"index\":377104,\"rxn_smiles\":\"C1COCCO1.CP(C)C.O.[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21>>NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"procedure_details\":\"Azide 23 (Example 10, 100 mg, 0.23 mmol) is dissolved in 0.9 mL of 1,4-dioxane\\/H2O (8:1), and 0.3 mL of a trimethylphospine solution (1 M in THF) is added. The reaction is stirred at room temperature for 3 h, then all volatiles are removed in vacuo. The crude product is purified by flash column chromatography with dichloromethane\\/methanol (95:5 to 10:1). Yield: 87 mg (0.021 mmol, 91%).\",\"reactant_000\":\"[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9947761297225952,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"rxn_str\":\"[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][N:14]=[N+]=[N-])=[C:4]([O:17][CH2:18][C:19]2[CH:32]=[CH:31][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)[N:3]=1.CP(C)C>O1CCOCC1.O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][NH2:14])=[C:4]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:27])([F:29])[F:28])=[CH:31][CH:32]=2)[N:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.005546689033508301,\"rxn_id\":\"ord-be83b62c5d5249cf938c714d7117d666\",\"index\":193745,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1>>NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"procedure_details\":\"To a solution of (S)-2-[[1-(2-azidoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid (6.28 g, 12.11 mmol) in THF (91 mL) was added a solution of trimethylphosphine in THF (48.5 mL, 48.46 mmol, 1.0M) at 0° C. It was a clear solution in the beginning and after 30 min some precipitate was formed and this mixture was stirred for overnight at which time TLC analysis of the mixture indicated the absence of starting material. Then, 10 equiv. of water (120 mmol, 2.16 mL) was added and the mixture was stirred for 2 h at room temperature. The solvent was removed under vacuum and the residue was azeotrophed two times with toluene to give a pasty material which was purified using HPLC to obtain 4.57 g (77% yield) of (S)-2-[[1-(2-aminoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid as an amorphous white solid. ES(+)-HRMS m\\/e calcd. for C24H27Cl2N3O4 (M+H)+ 492.1452, obsd. 492.1451.\",\"reactant_000\":\"[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9944533109664917,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"rxn_str\":\"[N:1]([CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:21][CH:20]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:23][CH:24]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1\",\"yield_000\":76.6}]","literatureScore":1,"label":"TTL ALL>>167","id":167},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008967578411102295,\"rxn_id\":\"ord-cf2e4e3955c04b01a2130e020e40723c\",\"index\":264007,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-4-fluorophenylamine (1.67 g, 4.87 mmoles) and sodium azide (0.38 g, 5.84 mmoles) in DMSO (20 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (1.44 g, 4.14 mmoles).\",\"reactant_000\":\"Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9910324215888977,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([O:18][CH2:19][CH2:20]Cl)[C:12]=2[NH2:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>CS(C)=O.O>[N:23]([CH2:20][CH2:19][O:18][C:13]1[CH:14]=[C:15]([F:17])[CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:22])=[N+:24]=[N-:25]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CCOC(C)=O\",\"distance\":0.00959622859954834,\"rxn_id\":\"ord-693a2494d2a64d6e84f87595007867e9\",\"index\":765833,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc(OCCCCl)cc1CO.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"procedure_details\":\"DMF (7.5 mL) was added to (5-(3-chloropropoxy)-2-nitrophenyl)methanol (635 mg, 0.00258 moles) and sodium azide (252 mg, 0.00387 moles) in a flask, and the resulting mixture was heated to 70° C. and stirred overnight. The reaction was diluted in ethyl acetate (100 mL) and washed twice with water (75 mL each) and once with brine (75 mL). The organic layer was dried with anhydrous magnesium sulfate, which was filtered out. The filtrate was concentrated on a rotary evaporator and dried in vacuo overnight to yield (5-(3-azidopropoxy)-2-nitrophenyl)methanol as a yellow solid (yield 88%). H NMR (400 MHz, CD2Cl2) δ 8.16 (d, J=9.1 Hz, 1H), 7.27 (d, J=2.8 Hz, 1H), 6.91 (dd, J=9.1, 2.8 Hz, 1H), 4.98 (s, 2H), 4.18 (t, J=6.0 Hz, 2H), 3.53 (t, J=6.6 Hz, 2H), 2.12-2.06 (m, 2H). 13C-NMR (100 MHz, CD2Cl2) δ 163.99, 141.22, 128.43, 114.97, 113.93, 66.15, 63.26, 48.68, 29.13 HRMS m\\/z: calculated for C10H12N4O4 [M+H]+, 253.0931. found, 253.0939.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCCCCl)cc1CO\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9904037714004517,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"rxn_str\":\"CN(C=O)C.Cl[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>C(OCC)(=O)C>[N:22]([CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1)=[N+:23]=[N-:24]\",\"yield_000\":88.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CS(C)=O\",\"distance\":0.009707868099212646,\"rxn_id\":\"ord-ed6541dc83464b24a92f34950c9068d0\",\"index\":137604,\"rxn_smiles\":\"CS(C)=O.O.O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"procedure_details\":\"A mixture of 6-(2-chloro-ethoxy)-3-(naphthalene-1-sulfonyl)-1-H-indazole (0.19 g, 0.5 mmoles) and sodium azide (0.04 g, 0.62 mmoles) in DMSO (2 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.17 g, 0.45 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9902921319007874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1.[N-:27]=[N+:28]=[N-:29].[Na+]>CS(C)=O.O>[N:27]([CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1)=[N+:28]=[N-:29]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.010035336017608643,\"rxn_id\":\"ord-dc8e8747d9b6443687f6f629e49ca7d3\",\"index\":120480,\"rxn_smiles\":\"CN(C)C=O.Nc1ncnc2c1ncn2CCCCl.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"procedure_details\":\"A mixture of 9-(3-chloropropyl)adenine and sodium azide in DMF was stirred at 80° C. for 24 hours, cooled to room temperature and filtered. The solid was washed with CH2Cl2. The solvent was removed from the combined filtrates and the residue was taken up in water with sonication. The aqueous layer was extracted with CH2Cl2. After removing the solvent, the crude product was recrystallized from ethanol to give 9-(3-azidopropyl)adenine as a white crystalline solid.\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1ncnc2c1ncn2CCCCl\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9899646639823914,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14].[N-:15]=[N+:16]=[N-:17].[Na+]>CN(C=O)C>[N:15]([CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14])=[N+:16]=[N-:17]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.010115861892700195,\"rxn_id\":\"ord-5c4de244180f41a2bbc87a484238a728\",\"index\":335449,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-phenylamine (0.5 g, 1.53 mmoles) and sodium azide (0.15 g, 2.29 mmoles) in DMSO (10 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.39 g, 1.17 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9898841381072998,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19]Cl)[C:12]=2[NH2:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>CS(C)=O.O>[N:22]([CH2:19][CH2:18][O:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:21])=[N+:23]=[N-:24]\",\"yield_000\":null}]","literatureScore":0.99,"label":"ER UA TTL ALL>>672","id":672},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":8,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":163}]},{"depth":8,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":163}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":163}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":7,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":163}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":163}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":163}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.6,"id":165,"pathId":163}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL>>990","id":990},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"JUINSXZKUKVTMD","smiles":"N=[N+]=[N-]","intrinsicScore":0.6,"id":990,"pathId":163}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"FCEJYNJLOZLCCR","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1OCCCN=[N+]=[N-]","intrinsicScore":0.3,"id":672,"pathId":163}],"RXN":"[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4]Cl)[N+:27](=[O:28])[O-:29])[Cl:24])[F:21].[NH:3]=[N+:1]=[N-:2]>>[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4][N:3]=[N+:1]=[N-:2])[N+:27](=[O:28])[O-:29])[Cl:24])[F:21];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NGGHYTSBRHGJPA","smiles":"NCCCOC1=C(C=C2C(NC3=CC=C(F)C(Cl)=C3)=NC=NC2=C1)[N+]([O-])=O","intrinsicScore":0.051,"id":167,"pathId":163}],"RXN":"[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][N:20]=[N+]=[N-])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27]>C1CCOC1.C(OCC)(C)=O.CP(C)C.O>[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][NH2:20])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27];9.7.13;Azido"},{"depth":3,"reaction":{"label":"TTL ALL>>51","id":51},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"FOZVXADQAHVUSV","smiles":"BrCCOCCBr","intrinsicScore":0.051,"id":51,"pathId":163}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":163}],"RXN":"[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][NH2:8])[N+:30](=[O:31])[O-:32])[Cl:29])[F:26].[CH2:2]([CH2:1]Br)[O:3][CH2:4][CH2:5]Br>N#CC.[O-]C(=O)[O-].[I-].[K+]>[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][N:8]4[CH2:1][CH2:2][O:3][CH2:4][CH2:5]4)[N+:30](=[O:31])[O-:32])[Cl:29])[F:26];4.2.5;Morpholine"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":163}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":163}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":163}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.55","depth":0,"reaction":{"label":">>0","id":0,"pathId":1498},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.002541661262512207,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9974583387374878,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0028268098831176758,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9971731901168823,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004594266414642334,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9954057335853577,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.005057811737060547,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9949421882629395,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005131185054779053,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.994868814945221,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.011910438537597656,\"rxn_id\":\"ord-15b1702fbf2942d89bcd0a818d72a147\",\"index\":127125,\"rxn_smiles\":\"Nc1ccc(F)c(Cl)c1.O=P(Cl)(Cl)Cl.Oc1ncnc2[nH]c(-c3ccccn3)cc12>>Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"procedure_details\":\"Under a protective gas, 20 mg (0.09 mmol) of 6-(pyrid-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (see Step 1.2) are heated at boiling with 1 ml of phosphorus oxychloride for 30 min. The reaction mixture is concentrated to dryness by evaporation and made into a suspension in 1 ml of n-butanol. 16.4 mg (0.108 mmol) of 3-chloro-4-fluoro-aniline are added and the suspension is boiled under reflux for 2 hours. The dark-brown suspension is then concentrated by evaporation and the residue is dissolved in methanol. Silica gel is added and drying is carried out. The powder is applied to a silica gel column and elution is carried out with ethyl acetate, yielding the title compound; 1H-NMR (400 MHz, DMSO-d6): 12.5 (sb, HN), 9.64 (s, HN), 8.64 (d, J=5, 1H), 8.38 (s, 1H), 8.35 (dd, J1 =7, J2 =3, 1H), 7.92 (m, 2H), 7.83 (m, 1H), 7.53 (s, 1H), 7.41 (t, J=9, 1H), 7.33 (m, 1H); HPLC: tRet (Grad20)=10.4 min; MS: (M)+ =339.\",\"reactant_000\":\"Oc1ncnc2[nH]c(-c3ccccn3)cc12\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9880895614624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Fc1ccc(Nc2ncnc3[nH]c(-c4ccccn4)cc23)cc1Cl\",\"rxn_str\":\"[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:16][C:10]2[N:11]=[CH:12][N:13]=[C:14](O)[C:9]=2[CH:8]=1.P(Cl)(Cl)(Cl)=O.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>>[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH:26][C:14]1[C:9]2[CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[NH:16][C:10]=2[N:11]=[CH:12][N:13]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016135811805725098,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838641881942749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.016157150268554688,\"rxn_id\":\"ord-2cb6311142fc45b1b9bfcc31a61197bd\",\"index\":218272,\"rxn_smiles\":\"Cc1cc(N)n[nH]1.Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1>>Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"procedure_details\":\"Starting materials: 4-hydroxy-6-trifluoromethyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 37) and 3-amino-5-methyl-1H-pyrazole.\",\"reactant_000\":\"Oc1cc(C(F)(F)F)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc(N)n[nH]1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838428497314453,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc(Nc2cc(C(F)(F)F)nc(N3CCCC3c3cc(-c4ccccn4)no3)n2)n[nH]1\",\"rxn_str\":\"O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:18]=2)[N:3]=1.[NH2:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1>>[CH3:34][C:32]1[NH:31][N:30]=[C:29]([NH:28][C:2]2[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[N:5]=[C:4]([N:12]3[CH2:16][CH2:15][CH2:14][CH:13]3[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:18]=3)[N:3]=2)[CH:33]=1\",\"yield_000\":null},{\"solvent_000\":\"O=P(Cl)(Cl)Cl\",\"solvent_001\":null,\"distance\":0.016196131706237793,\"rxn_id\":\"ord-8fad4c54814d4a32a51ffc32e4c439f7\",\"index\":521100,\"rxn_smiles\":\"NC1Cc2ccccc2C1.O=P(Cl)(Cl)Cl.Oc1ncnc2ccsc12>>c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"procedure_details\":\"Using 4-hydroxythieno[3,2-d]pyrimidine (60 mg, 0.39 mmol), and phosphorus oxychloride (0.6 ml), and then 2-aminoindan (210 mg, 1.56 mmol), a similar procedure to Example 5 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to obtain the title compound (30 mg, 0.11 mmol) having the following physical properties:\",\"reactant_000\":\"Oc1ncnc2ccsc12\",\"reactant_002\":null,\"reactant_001\":\"NC1Cc2ccccc2C1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9838038682937622,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"c1ccc2c(c1)CC(Nc1ncnc3ccsc13)C2\",\"rxn_str\":\"O[C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1>>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":28.2},{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":null,\"distance\":0.0167691707611084,\"rxn_id\":\"ord-58567da7d1834ce8bdf19dbc08b3156b\",\"index\":277584,\"rxn_smiles\":\"Cc1cc2ncnc(O)c2cn1.Cl.Nc1cccc(Cl)c1.c1ccncc1>>Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1.Cl\",\"procedure_details\":\"Utilizing a procedure analogous to that described in Example 16, this product was prepared in 34% yield from 4-hydroxy-7-methyl-pyrido[4,3-d]pyrimidine (1.0 eq) and m-chloroaniline (40.0 eq) in pyridine. The HCl salt was generated from the purified free base according to the procedure given in Example 1. (M.P. 255-256° C.; GC-MS: 270 (MH+); anal. RP18-HPLC RT: 4.05 min.)\",\"reactant_000\":\"Cc1cc2ncnc(O)c2cn1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9832308292388916,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cc2ncnc(Nc3cccc(Cl)c3)c2cn1\",\"rxn_str\":\"O[C:2]1[C:3]2[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].Cl>N1C=CC=CC=1>[ClH:13].[Cl:13][C:14]1[CH:15]=[C:16]([NH:17][C:2]2[C:3]3[CH:11]=[N:10][C:9]([CH3:12])=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:18]=[CH:19][CH:20]=1\",\"yield_000\":34.0}]","literatureScore":0.99,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 UA ALL>>977","id":977},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"KCORZHJVTZIZFD","smiles":"OC1=NC=NC2=CC(F)=CC=C12","intrinsicScore":0.19,"id":977,"pathId":1498}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":1498}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":1498}],"RXN":"[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH2:14])[Cl:19])[F:20].[cH:3]1[cH:2][c:1]2[c:6]([cH:5][c:4]1[F:11])[n:7][cH:8][n:9][c:10]2O>>[cH:15]1[cH:16][c:17]([c:18]([cH:12][c:13]1[NH:14][c:10]2[c:1]3[cH:2][cH:3][c:4]([cH:5][c:6]3[n:7][cH:8][n:9]2)[F:11])[Cl:19])[F:20];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":1498}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.6,"id":159,"pathId":1498}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"UA ALL>>43","id":43},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VZKSLWJLGAGPIU","smiles":"OCCCN1CCOCC1","intrinsicScore":0.42,"id":43,"pathId":1498}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":1498}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)F)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:28]1[CH2:29][O:30][CH2:31][CH2:32][N:27]1[CH2:23][CH2:24][CH2:25][OH:26]>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:26][CH2:25][CH2:24][CH2:23][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1498}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1498}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1498}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1498}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1498}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.563","depth":0,"reaction":{"label":">>0","id":0,"pathId":711},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":711}]},{"depth":7,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":711}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":711}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":711}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":711}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":711}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":711}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":711}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":711}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":711}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":711}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":711}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":711}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.633","depth":0,"reaction":{"label":">>0","id":0,"pathId":731},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.004738807678222656,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9952611923217773,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.005608558654785156,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9943914413452148,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.005852222442626953,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.994147777557373,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006216287612915039,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.993783712387085,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.006459832191467285,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9935401678085327,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":731}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":731}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":731}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":731}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.33,"id":159,"pathId":731}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"ER ALL>>85","id":85},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RQFUZUMFPRMVDX","smiles":"OCCCBr","intrinsicScore":0.7,"id":85,"pathId":731}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":731}],"RXN":"[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)F)[N+:2](=[O:1])[O-:22])[Cl:20])[F:18].[CH2:24]([CH2:25][OH:26])[CH2:23][Br:27]>>[cH:15]1[cH:16][c:17]([c:19]([cH:21][c:14]1[NH:13][c:12]2[c:5]3[cH:4][c:3]([c:8]([cH:7][c:6]3[n:9][cH:10][n:11]2)[O:26][CH2:25][CH2:24][CH2:23][Br:27])[N+:2](=[O:1])[O-:22])[Cl:20])[F:18];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":731}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":731}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":731}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":731}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":731}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":731}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.67","depth":0,"reaction":{"label":">>0","id":0,"pathId":2134},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037958621978759766,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.996204137802124,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0050907135009765625,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9949092864990234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.005206882953643799,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9947931170463562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005465328693389893,\"rxn_id\":\"ord-2ce24cbe9e6e480c91a0d7bffb61ebba\",\"index\":738150,\"rxn_smiles\":\"C1COCCN1.CC(C)(C)ON=c1cc(-c2cc3cccn3cn2)oc2cc(OCCCCl)ccc12>>CC(C)(C)ON=c1cc(-c2cc3cccn3cn2)oc2cc(OCCCN3CCOCC3)ccc12\",\"procedure_details\":\"7-(3-Morpholin-4-yl-propoxy)-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl-oxime was prepared in 55% yield using the method described in example 87A, starting from 7-(3-Chloro-propoxy)-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl oxime (example 143B) and morpholine.\",\"reactant_000\":\"CC(C)(C)ON=c1cc(-c2cc3cccn3cn2)oc2cc(OCCCCl)ccc12\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945346713066101,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)ON=c1cc(-c2cc3cccn3cn2)oc2cc(OCCCN3CCOCC3)ccc12\",\"rxn_str\":\"[C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][CH2:20]Cl)=[CH:14][CH:15]=2)[O:10][C:9]([C:22]2[N:27]=[CH:26][N:25]3[CH:28]=[CH:29][CH:30]=[C:24]3[CH:23]=2)=[CH:8]1)([CH3:4])([CH3:3])[CH3:2].[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>>[C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][CH2:20][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[CH:14][CH:15]=2)[O:10][C:9]([C:22]2[N:27]=[CH:26][N:25]3[CH:28]=[CH:29][CH:30]=[C:24]3[CH:23]=2)=[CH:8]1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":55.0},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.005742847919464111,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9942571520805359,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0}]","literatureScore":1,"label":"TTL ALL>>16","id":16},"children":[{"depth":2,"reaction":{"scalabilityModelScore":6.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.06608951091766357,\"rxn_id\":\"ord-9b239ee410874131801acfbc5a613f8b\",\"index\":208806,\"rxn_smiles\":\"CC=CC(=O)Cl.ClCCl.NC(=O)c1cc(Cl)ccc1N>>C=C(C)C(=O)Nc1ccc(Cl)cc1C(N)=O\",\"procedure_details\":\"2-Amino-5-chloro-benzamide (2.5 mmoL), a literature known compound, was treated with TEA (3.0 mmoL) followed by methylacryl chloride (2.5 mmoL) in DCM at 0° C. The reaction was slowly warmed to room temperature and kept for another 2 h. The reaction mixture was then partitioned between DCM and water. The organic layer was washed with sat. Na2CO3, brine, dried over anhydrous Na2SO4, filtered, concentrated and purified by silica gel column chromatography to afford the title compound as a white solid.\",\"reactant_000\":\"CC=CC(=O)Cl\",\"reactant_002\":\"ClCCl\",\"reactant_001\":\"NC(=O)c1cc(Cl)ccc1N\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9339104890823364,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"C=C(C)C(=O)Nc1ccc(Cl)cc1C(N)=O\",\"rxn_str\":\"[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].C[CH:13]=[CH:14][C:15](Cl)=[O:16].[CH2:18](Cl)Cl>>[Cl:11][C:8]1[CH:9]=[CH:10][C:2]([NH:1][C:15](=[O:16])[C:14]([CH3:18])=[CH2:13])=[C:3]([CH:7]=1)[C:4]([NH2:6])=[O:5]\",\"yield_000\":null},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"ClCCl\",\"distance\":0.07079339027404785,\"rxn_id\":\"ord-60d9061fa3f543a2a9376bc8387bb8c1\",\"index\":66111,\"rxn_smiles\":\"C=C(Cl)C(=O)O.CCN(CC)CC.COC(=O)[C@@H](N)Cc1c[nH]cn1.Cl.Cl.ClCCl>>C=CC(=O)N[C@@H](Cc1c[nH]cn1)C(=O)OC\",\"procedure_details\":\"After chloroacrylic acid (1.6 ml, 20 mmol) was dropped, with ice cooling, into a solution of histidine methyl ester dihydrochloride (6.05 g, 25 mmol) and triethylamine (14 mL, 100 mmol) in methylene chloride (200 mL), the same operation as in the synthesis of N(α)-acryloyl-N(π)-methyl-L-histidine methyl ester was conducted to give N(α)-acryloyl-L-histidine methyl ester (2.0 g, 36%) as an oily product.\",\"reactant_000\":\"COC(=O)[C@@H](N)Cc1c[nH]cn1\",\"reactant_002\":null,\"reactant_001\":\"C=C(Cl)C(=O)O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9292066097259521,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"C=CC(=O)N[C@@H](Cc1c[nH]cn1)C(=O)OC\",\"rxn_str\":\"Cl[C:2](=[CH2:6])[C:3](O)=[O:4].Cl.Cl.[CH3:9][O:10][C:11](=[O:20])[C@H:12]([CH2:14][C:15]1[N:19]=[CH:18][NH:17][CH:16]=1)[NH2:13].C(N(CC)CC)C>C(Cl)Cl>[CH3:9][O:10][C:11](=[O:20])[C@H:12]([CH2:14][C:15]1[N:19]=[CH:18][NH:17][CH:16]=1)[NH:13][C:3](=[O:4])[CH:2]=[CH2:6]\",\"yield_000\":44.8},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CN1CCCC1=O\",\"distance\":0.07334160804748535,\"rxn_id\":\"ord-f206d1ea171946c7839ab8165e95848b\",\"index\":522923,\"rxn_smiles\":\"CN(C)C\\/C=C\\/C(=O)Cl.CN1CCCC1=O.ClCCl.Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1>>CC=CC(=O)Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1\",\"procedure_details\":\"To a stirred solution of N2-(6-(4-phenoxyphenoxy)pyrimidin-4-yl)pyridine-2,6-diamine (0.65 g, 1.75 mmol) in NMP (10 mL) was added dimethylaminocrotonyl chloride (1.026 g, 7 mmol) at 0° C. The reaction mixture was allowed to come to room temperature and kept at it for 1 h. It was diluted with dichloromethane (10 mL), was washed with NaHCO3 solution (2 mL) and water (2 mL), and dried over Na2SO4. The dichloromethane solution was filtered and was concentrated under reduced pressure to give a residue that was purified by column chromatography (SiO2, 60-120, chloroform\\/methanol, 9\\/1) to give (E)-4-dimethylamino)-N-(6-(6-(4-phenoxyphenoxy)pyrimidin-4-ylamino)pyridin-2-yl)but-2-enamide (I-82) as an off white solid. 1H NMR (DMSO-d6) δ ppm: 2.19 (s, 6H), 3.08 (d, J=5.52 Hz, 2H), 6.50 (d, J=15.4 Hz, 1H), 6.77 (td, J=5.92 & 15.4 Hz, 1H), 7.00-7.07 (m, 5H), 7.15 (t, J=7.36 Hz, 1H), 7.21 (dd, J=2.2 & 8.92 Hz, 2H), 7.41 (t, J=7.52 Hz, 2H), 7.68 (t, J=7.96 Hz, 1H), 7.77 (d, J=7.96 Hz, 1H), 7.95 (s, 1H), 8.35 (s, 1H), 10.20 (s, 1H), 10.40 (s, 1H); LCMS: m\\/e 483 (M+1).\",\"reactant_000\":\"Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1\",\"reactant_002\":null,\"reactant_001\":\"CN(C)C\\/C=C\\/C(=O)Cl\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9266583919525146,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC=CC(=O)Nc1cccc(Nc2cc(Oc3ccc(Oc4ccccc4)cc3)ncn2)n1\",\"rxn_str\":\"[O:1]([C:8]1[CH:28]=[CH:27][C:11]([O:12][C:13]2[N:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([NH2:26])[N:21]=3)[CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN([CH2:32]\\/[CH:33]=[CH:34]\\/[C:35](Cl)=[O:36])C>CN1C(=O)CCC1.ClCCl>[O:1]([C:8]1[CH:28]=[CH:27][C:11]([O:12][C:13]2[N:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[N:21]=[C:22]([NH:26][C:35](=[O:36])[CH:34]=[CH:33][CH3:32])[CH:23]=[CH:24][CH:25]=3)[CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.07634156942367554,\"rxn_id\":\"ord-37af189c9f074f43975d0a666e77eed4\",\"index\":74200,\"rxn_smiles\":\"COC(=O)C1CC2C=CC1O2.Cl.Nc1ccccc1.O>>C=CC(=O)Nc1ccccc1\",\"procedure_details\":\"7.2 parts 30% methanolic Na-methylate solution are added to 46.5 parts aniline. 77 parts 2-carbomethoxy-7-oxabicyclo(2,2,1)hept-5-ene are added drop-wise at 40° C. The reaction medium is then stirred for 15 hours at this temperature and neutralised with 4 parts concentrated hydrochloric acid. 50 parts water are added, and the organic phase separated off. The organic phase is reduced in a rotary evaporator at a bath temperature of 90° C. and under a vacuum of 20 Torr. The residue is heated in a vacuum of 20 Torr to 110° to 120° C. (bath temperature 140° C.). On conclusion of the furane separation, the sedimentation temperature increases and the product distills over. 27.5 parts N-phenylacrylamide with a boiling point of 135° C. at 0.4 Torr are obtained. The product recrystallised from the acetonitrile at -20° C. has a melting point of 114° to 115° C.\",\"reactant_000\":\"Nc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"COC(=O)C1CC2C=CC1O2\",\"rxn_time\":15.0,\"reactant_003\":null,\"similarity\":0.9236584305763245,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"C=CC(=O)Nc1ccccc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:8]([CH:12]1CC2O[CH:13]1C=C2)(OC)=[O:9].Cl>O>[C:2]1([NH:1][C:8](=[O:9])[CH:12]=[CH2:13])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CC#N\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.08093816041946411,\"rxn_id\":\"ord-5f64f7331f114d09a892ddee5f9bd4b8\",\"index\":490819,\"rxn_smiles\":\"CC#N.CC(C)\\/C=C\\/C(=O)O.CCN(CC)CC.CN(C)C(On1nnc2ccccc21)=[N+](C)C.Cc1cc(NCCN)c2ccccc2n1.F[P-](F)(F)(F)(F)F>>C\\/C=C\\/C(=O)NCCNc1cc(C)nc2ccccc12\",\"procedure_details\":\"(E)-4-Methylpent-2-enoic acid (190 mg, 1.3 mmol) was mixed together with HBTU (470 mg, 1.3 mmol) and N-(2-methyl-4-quinolyl)ethane-1,2-diamine (250 mg, 1.2 mmol) in acetonitrile (5 ml). Triethylamine (1 mll) was added with stirring at 0° C. over 15 minutes and the resulting mixture was stirred at room temperature overnight. The volatiles were removed under reduced pressure, the residue was dissolved in DCM and washed with a saturated solution of sodium bicarbonate. The combined aqueous solutions were extracted three times with DCM. The organic layers were combined, dried over sodium sulfate, the solvent was removed under reduced pressure to give 245 mg of a yellow solid (0.82 mmol, 66%). MS (APCI) m\\/z=298.2 [M+1]+.\",\"reactant_000\":\"Cc1cc(NCCN)c2ccccc2n1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)\\/C=C\\/C(=O)O\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9190618395805359,\"agent_000\":\"CN(C)C(On1nnc2ccccc21)=[N+](C)C\",\"agent_001\":\"F[P-](F)(F)(F)(F)F\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"C\\/C=C\\/C(=O)NCCNc1cc(C)nc2ccccc12\",\"rxn_str\":\"C[CH:2](C)\\/[CH:3]=[CH:4]\\/[C:5](O)=[O:6].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:33][C:34]1[CH:43]=[C:42]([NH:44][CH2:45][CH2:46][NH2:47])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:35]=1.C(N(CC)CC)C>C(#N)C>[CH3:33][C:34]1[CH:43]=[C:42]([NH:44][CH2:45][CH2:46][NH:47][C:5](=[O:6])\\/[CH:4]=[CH:3]\\/[CH3:2])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:35]=1\",\"yield_000\":68.3}]","literatureScore":0.93,"label":"UA TTL ALL>>40","id":40},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.014116823673248291,\"rxn_id\":\"ord-6288fabec59447a0a99e96050f5437c2\",\"index\":600781,\"rxn_smiles\":\"C1CCOC1.Cl.O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1.[Na+].[OH-]>>Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"procedure_details\":\"A solution of 602 mg (1.28 mmol) of N-[3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propyl]-3,5-dinitro-benzenesulfonamide in 10 ml of THF is mixed at room temperature with 4.2 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid. After 2 hours, it is mixed again with 3.0 ml of a 15% solution of Ti(III)Cl in approximately 10% hydrochloric acid, and it is stirred for another 16 hours. The batch is made basic with 2N NaOH solution and filtered. The filter cake is rewashed with THF and water. The THF of the filtrate is drawn off on a rotary evaporator, and the residue is extracted from ethyl acetate. The combined organic phases are filtered through a Whatman filter and concentrated by evaporation. 440 mg (0.95 mmol, corresponding to 74% of theory) of the product is obtained.\",\"reactant_000\":\"O=[N+]([O-])c1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9858831763267517,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"Nc1cc([N+](=O)[O-])cc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1\",\"rxn_str\":\"[Br:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([N+:26]([O-:28])=[O:27])[CH:18]=2)(=[O:16])=[O:15])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.Cl>[NH2:23][C:21]1[CH:22]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)(=[O:15])=[O:16])[CH:18]=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.016109049320220947,\"rxn_id\":\"ord-343c4847648a4856a864df6efa893e73\",\"index\":553945,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2>>Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"procedure_details\":\"Compound 5,6-dinitrobenzo[d][1,3]dioxole (6.0 g, 28.3 mmol) was added to stirred glacial acetic acid (120 mL) under N2 atmosphere. After the mixture was heated to boiling, the heat source was removed and iron powder (4.75 g) added with vigorous stirring. Quick spontaneous boiling occurred, the mixture turned dark and the exothermic reaction subsided (2˜5 min). The mixture was refluxed for 10 min and poured into ice\\/water. The orange-red product was isolated by filtration, dissolved in glacial acetic acid, and the solution filtered while hot. The filtrate was poured into ice-cold water. The orange-red solid product was isolated by filtration and dried to provide compound 6-nitrobenzo[d][1,3]dioxol-5-amine (4.35 g, 84%). LCMS: 183 [M+1]+; 1H NMR (DMSO-d6) δ 6.06 (s, 2H), 6.51 (s, 1H), 7.36 (s, 1H), 7.73 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(cc1[N+](=O)[O-])OCO2\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.983890950679779,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1cc2c(cc1[N+](=O)[O-])OCO2\",\"rxn_str\":\"[N+:1]([C:4]1[C:12]([N+:13]([O-])=O)=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]>C(O)(=O)C>[N+:1]([C:4]1[C:12]([NH2:13])=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]\",\"yield_000\":84.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01629471778869629,\"rxn_id\":\"ord-8a53d7ca8b7f426e98b8ed828ac03699\",\"index\":461085,\"rxn_smiles\":\"N.O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1.[Na].[Na][Na]>>Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"procedure_details\":\"An aqueous solution of the disodium salt of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is treated with an equivalent amount, relative to the nitro group to be reduced, of sodium bisulphide solution at 75°-85° C., ammonia being added. The course of the reaction can be followed by known analytical methods. When the partial reduction has ended, the 4-nitro-4'-amino-stilbene-2,2'-disulphonic acid formed is isolated as the disodium salt or as an inner salt. The amount of 4,4'-diamino-stilbene-2,2'-disulphonic acid contained as an impurity is less than 1% and the residual content of 4,4'-dinitro-stilbene-2,2'-disulphonic acid is less than 0.1%. 4-Nitro-4'-aminostilbene-2,2'-disulphonic acid is a known intermediate product for dyestuffs.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9837052822113037,\"agent_000\":\"N\",\"agent_001\":\"[Na]\",\"agent_002\":\"[Na][Na]\",\"temperature\":null,\"product_000\":\"Nc1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1\",\"rxn_str\":\"[Na][Na].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([OH:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-])=O.[Na].N>>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:24])=[O:25])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([NH2:3])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.017170846462249756,\"rxn_id\":\"ord-4a44648623804c978438a370eb54194d\",\"index\":732100,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1>>Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"procedure_details\":\"A suspension of 2,7-dinitro-naphthalene in ethylacetate (400 ml) and DMF (4 ml) was hydrogenated over P\\/C at 50° C. for 2 hours. After work-up and purification by chromatography 2.1 g (11.2 mmol, 24%) of the title compound, MS: m\\/e=251(M+) was obtained.\",\"reactant_000\":\"O=[N+]([O-])c1ccc2ccc([N+](=O)[O-])cc2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9828291535377502,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ccc([N+](=O)[O-])cc2c1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][C:8]([N+:14]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=1)([O-:3])=[O:2]>C(OC(=O)C)C.CN(C=O)C>[NH2:14][C:8]1[CH:7]=[C:6]2[C:11]([CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]2)=[CH:10][CH:9]=1\",\"yield_000\":24.0},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.018261253833770752,\"rxn_id\":\"ord-753a8f480966446dafb69e87c8975f55\",\"index\":108247,\"rxn_smiles\":\"CC(=O)O.O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1.[Fe]>>Nc1cc(Br)cc([N+](=O)[O-])c1\",\"procedure_details\":\"To a solution of 1-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid (120 ml) at 90° C. was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portionwise over a period of 30 min (caution: highly exothermic reaction). After completion of the addition, the mixture was quenched by the addition of crushed ice. The precipitate formed was filtered and was washed with cold water to obtain orange solid. The solid was dried under vacuum to give the product in 80% yield (14 g). 1H NMR (300 MHz, CDCl3): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9817387461662292,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Br)cc([N+](=O)[O-])c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]\",\"yield_000\":80.0}]","literatureScore":0.99,"label":"AT ER UA TTL ALL>>173","id":173},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.2,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.026102662086486816,\"rxn_id\":\"ord-d4eb54fb6b5d4262974d2dd755035f68\",\"index\":655647,\"rxn_smiles\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1.[Na+].[O-]C1CCCC1>>CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"procedure_details\":\"0.12 mmol of (6-Ethoxy-2-fluoro-3-methanesulfonyl-phenyl)-[4-(4-methanesulfonyl-phenyl)-piperazin-1-yl]-methanone (example 55) was added to a solution of sodium cyclopentanolate (prepared from 1 mmol sodium dissolved in 1 ml of cyclopentanol). The mixture was heated for 1 hour at 80° C., poured on ice\\/water and extracted with ethyl acetate. Chromatography (SiO2; ethyl acetate) yielded the title compound as a slightly yellow solid. MS (m\\/e): 551.1 (MH+, 29%)\",\"reactant_000\":\"CCOc1ccc(S(C)(=O)=O)c(F)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"[O-]C1CCCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9738973379135132,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"CCOc1ccc(S(C)(=O)=O)c(OC2CCCC2)c1C(=O)N1CCN(c2ccc(S(C)(=O)=O)cc2)CC1\",\"rxn_str\":\"[CH2:1]([O:3][C:4]1[C:9]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:8](F)[C:7]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:6][CH:5]=1)[CH3:2].[CH:33]1([O-:38])[CH2:37][CH2:36][CH2:35][CH2:34]1.[Na+]>>[CH:33]1([O:38][C:8]2[C:7]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:6][CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:22][CH:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:37][CH2:36][CH2:35][CH2:34]1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02665776014328003,\"rxn_id\":\"ord-a516cb92ae8746a197bb955ab0b27301\",\"index\":284459,\"rxn_smiles\":\"C1CCOC1.CC(C)(C)[O-].CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21.COCO[C@H](C)CO.O=P(O)(O)O.[Na+]>>CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"procedure_details\":\"To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C\\u2014CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.\",\"reactant_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ccncc21\",\"reactant_002\":null,\"reactant_001\":\"COCO[C@H](C)CO\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.97334223985672,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"O=P(O)(O)O\",\"agent_002\":\"[Na+]\",\"temperature\":0.0,\"product_000\":\"CCCCn1\\/c(=N\\/C(=O)c2cc(C(F)(F)F)ccc2OC[C@@H](C)OCOC)sc2ccncc21\",\"rxn_str\":\"CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]\\/[C:20]\\/1=[N:28]\\\\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]\",\"yield_000\":73.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.027878761291503906,\"rxn_id\":\"ord-ef2930e60d9c4601802f454f0e231626\",\"index\":27985,\"rxn_smiles\":\"CC[O-].O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1.[Na+]>>CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"procedure_details\":\"Prepared by the method of Example 40a), from 2-(5-nitro-2-fluorophenyl)-5-phenylbenzoxazole (200 mg, 0.60 mmol) and sodium ethoxide (41 mg, 0.61 mmol) the subtitle compound was obtained (197 mg, 91%). 1H NMR (DMSO) δ 8.92(d, 1H), 8.51(dd, 1H), 8.18(s, 1H), 7.95(d, 1H), 7.83(d, 2H), 7.56(t, 3H), 7.47(t, 3H), 4.50(q, 2H), 1.57(t, 3H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(-c2nc3cc(-c4ccccc4)ccc3o2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9721212387084961,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccccc3)ccc2o1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2].[O-:26][CH2:27][CH3:28].[Na+]>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH2:27][CH3:28])=[C:8]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][C:13]=3[N:14]=2)[CH:9]=1)([O-:3])=[O:2]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.028167724609375,\"rxn_id\":\"ord-6d561160e12244ba80148b30b4006f1c\",\"index\":371446,\"rxn_smiles\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F.O=C([O-])O.O=S1(=O)CCN(CCCO)CC1.[Na+].[Na]>>COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"procedure_details\":\"A mixture of sodium (48 mg, 2.1 mmol) in 2 mL of 3-(1,1-dioxothiomorpholinyl)-1-propanol (WO 20047212) is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 100° C. for 4 hours, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 88 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile, mp 118-120° C.\",\"reactant_000\":\"COc1cc2c(Nc3cc(OC)c(Cl)cc3Cl)c(C#N)cnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=S1(=O)CCN(CCCO)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.971832275390625,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[Na]\",\"temperature\":100.0,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c(Cl)cc1Cl\",\"rxn_str\":\"[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].C(=O)(O)[O-].[Na+].[O:33]=[S:34]1(=[O:44])[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][CH2:42][OH:43])[CH2:36][CH2:35]1>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:43][CH2:42][CH2:41][CH2:40][N:37]3[CH2:36][CH2:35][S:34](=[O:44])(=[O:33])[CH2:39][CH2:38]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.028632760047912598,\"rxn_id\":\"ord-46131189663c43019d2bd61871b560a2\",\"index\":670977,\"rxn_smiles\":\"C1CCOC1.CN(C)CC[O-].Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O.O.[Na+]>>Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"procedure_details\":\"To 160 mg of 6-fluoro-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere was added 3 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 3 hours, the reaction was diluted with water and the product extracted five times with chloroform. The crude product was purified by flash chromatography with 1% triethyl amine and 10% methanol\\/chloroform followed by recrystallized from chloroform\\/ether to give 106 mg of 6-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 100-180° C. (decomposed, effervescence); mass spectrum (m\\/e): M+H 419.9.\",\"reactant_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1O\",\"reactant_002\":null,\"reactant_001\":\"CN(C)CC[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9713672399520874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc(Nc2c(C#N)cnc3cnc(OCCN(C)C)cc23)cc1O\",\"rxn_str\":\"F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+]>O1CCCC1.O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:27][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1\",\"yield_000\":null}]","literatureScore":0.97,"label":"AT ER UA ALL>>486","id":486},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":\"ClCCl\",\"distance\":0.014608323574066162,\"rxn_id\":\"ord-bca3884431a644aa875cb5a1b98b5d46\",\"index\":305986,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.O=C(OC(=O)C(F)(F)F)C(F)(F)F.OO.[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.5 mL, ca. 10 mmol) was added dropwise to a stirred solution of TFAA (1.4 mL, 10 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 24 (246 mg, 1.0 mmol) and TFA (0.28 mL, 2.0 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 0° C. for 1 h and then at 20° C. for 30 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (5×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-4%) of MeOH\\/DCM, to give 1,4-dioxide 25 (106 mg, 40%) as a red solid: mp (MeOH\\/DCM) 187-188° C.; 1H NMR [(CD3)2SO] δ 7.99 (s, 1H, H-9), 7.92-7.98 (m, 2H, NH, H-5), 4.84 (t, J=6.0 Hz, 1H, OH)), 3.61 (q, J=6.0 Hz, 2H, CH2O), 3.46 (q, J=6.0 Hz, 2H, CH2N), 2.98-3.10 (m, 4H, H-6, H-8), 2.05-2.14 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 154.5, 149.4 144.9, 137.6, 129.0, 115.0, 110.9, 59.1, 43.1, 32.6, 31.7, 25.1. Anal. calcd for C12H14N4O3: C, 55.0; H, 5.4; N, 21.4. Found: C, 54.8; H, 5.4; N, 21.1%.\",\"reactant_000\":\"O=C(OC(=O)C(F)(F)F)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCO)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9853916764259338,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCO)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N:20]=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[O-:16][N+:17]1[C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][C:21]=2[N+:20]([O-:4])=[C:19]([NH:30][CH2:31][CH2:32][OH:33])[N:18]=1)[CH2:27][CH2:26][CH2:25]3\",\"yield_000\":40.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015018701553344727,\"rxn_id\":\"ord-4ff619ff325c429299cdbd9b19c4b923\",\"index\":402034,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.63 mL, ca. 12.7 mmol) was added dropwise to a stirred solution of TFM (1.8 mL, 12.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 36 (397 mg, 1.3 mmol) and TFA (0.20 mL, 2.5 mmol) in DCM (20 mL) at 0° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 37 (241 mg, 57%) as a red solid: mp (MeOH\\/EtOAc) 165-168° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.08 (s, 1H, H-5), 7.43 (br s, 1H, NH), 3.60-3.64 (m, 2H, CH2N), 3.03-3.11 (m, 4H, H-6, H-8), 2.62 (t, J=6.0 Hz, 2H, CH2N), 2.42-2.47 (m, 4H, 2×CH2), 2.15-2.22 (m, 2H, H-7), 1.57-1.63 (m, 4H, 2×CH2), 1.41-1.47 (m, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 56.9, 54.4 (2), 38.2, 33.4, 32.4, 25.9 (2), 25.6, 24.3. Anal. calcd for C17H23N5O2.¼H2O: C, 61.2; H, 7.1; N, 21.0. Found: C, 60.7; H, 7.0; N, 21.0%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2cc3c(cc21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9849812984466553,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2cc3c(cc21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":56.3},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.015435934066772461,\"rxn_id\":\"ord-e947c30edcac4d5f85af4d0febdc8b90\",\"index\":315602,\"rxn_smiles\":\"CC(=O)O.O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1.OO>>O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"procedure_details\":\"A mixture of 67.5 g (0.213 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinoline (from Example 115), 36.3 g (0.32 mole) of 30% hydrogen peroxide and 450 ml of glacial acetic acid was heated at 65° C. for 2 days with stirring. The solution was evaporated in vacuo, and the residue was then added to water. The mixture was neutralized with aqueous sodium hydroxide solution and sodium bicarbonate. The solid was separated by filtration, washed with water and recrystallized form methanol to provide tan solid 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]-quinolin-5-oxide.\",\"reactant_000\":\"OO\",\"reactant_002\":null,\"reactant_001\":\"O=C(OCCn1cnc2cnc3ccccc3c21)c1ccccc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9845640659332275,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1\",\"rxn_str\":\"[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:25]O>C(O)(=O)C>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-:25])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015453338623046875,\"rxn_id\":\"ord-f7cd00cda9e24d8a82df13497d6a12d0\",\"index\":379376,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3>>[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"procedure_details\":\"H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM, to give 1,4-dioxide 13 (89 mg, 50%) as a red solid: mp (MeOH\\/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCN2CCCCC2)nc2ccc3c(c21)CCC3\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9845466613769531,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"[O-][n+]1nc(NCCN2CCCCC2)[n+]([O-])c2ccc3c(c21)CCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:27]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[C:24]4[CH2:23][CH2:22][CH2:21][C:20]=4[CH:19]=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1\",\"yield_000\":54.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.015593409538269043,\"rxn_id\":\"ord-e27814b7ebe141148c14ffaec3bee6f8\",\"index\":30729,\"rxn_smiles\":\"ClCCl.N.O=C(O)C(F)(F)F.OO.[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3>>[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"procedure_details\":\"H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH\\/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m\\/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m\\/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.\",\"reactant_000\":\"O=C(O)C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":\"[O-][n+]1nc(NCCCN2CCOCC2)nc2cc3c(cc21)OCC3\",\"rxn_time\":0.17,\"reactant_003\":null,\"similarity\":0.984406590461731,\"agent_000\":\"N\",\"agent_001\":\"OO\",\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"[O-][n+]1nc(NCCCN2CCOCC2)[n+]([O-])c2cc3c(cc21)OCC3\",\"rxn_str\":\"OO.[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N:18]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(O)(C(F)(F)F)=[O:28]>C(Cl)Cl.N>[N:3]1([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:22]=[C:21]4[O:23][CH2:24][CH2:25][C:20]4=[CH:19][C:17]=3[N+:18]=2[O-:28])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1\",\"yield_000\":13.5}]","literatureScore":0.99,"label":"AT LR UA TTL ALL>>487","id":487},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":2134}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":2134}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.53,"id":159,"pathId":2134}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 UA AT ALL>>590","id":590},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MHAJPDPJQMAIIY","smiles":"OO","intrinsicScore":0.53,"id":590,"pathId":2134}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HYLZKSWKESQZHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=C[N+]([O-])=C2C=C1F","intrinsicScore":0.35,"id":487,"pathId":2134}],"RXN":"[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n:10][cH:9][n:8]2)[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20].[OH:24]O>>[cH:17]1[cH:18][c:19]([c:21]([cH:22][c:16]1[NH:15][c:7]2[c:6]3[cH:5][c:4]([c:13]([cH:12][c:11]3[n+:10]([cH:9][n:8]2)[O-:24])[F:14])[N+:2](=[O:1])[O-:3])[Cl:23])[F:20];8.4.2;Nitrogen"},{"depth":5,"reaction":{"label":"LR UA TTL ALL>>941","id":941},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HUNZOBARCPLNPC","smiles":"[O-]CCCCl","intrinsicScore":0.073,"id":941,"pathId":2134}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"GLLGQTRKUUNDQD","smiles":"[O-][N+](=O)C1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.57,"id":486,"pathId":2134}],"RXN":"[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])F)[N+:2](=[O:1])[O-:3])[Cl:15])[F:13].[CH2:26]([CH2:25][O-:24])[CH2:27][Cl:28]>>[cH:10]1[cH:11][c:12]([c:14]([cH:16][c:9]1[NH:8][c:7]2[c:6]3[cH:5][c:4]([c:23]([cH:22][c:21]3[n+:19]([cH:18][n:17]2)[O-:20])[O:24][CH2:25][CH2:26][CH2:27][Cl:28])[N+:2](=[O:1])[O-:3])[Cl:15])[F:13];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YAIVOKCSYDYBSV","smiles":"NC1=C(OCCCCl)C=C2C(=C1)C(NC1=CC=C(F)C(Cl)=C1)=NC=[N+]2[O-]","intrinsicScore":0.49,"id":173,"pathId":2134}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[N+:8](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:10]3[cH:9][c:7]([c:6]([cH:5][c:4]3[n+:3]([cH:2][n:1]2)[O-:26])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[NH2:8])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"AT ER UA TTL ALL>>332","id":332},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OKOSPWNNXVDXKZ","smiles":"ClC(=O)CC=C","intrinsicScore":0.49,"id":332,"pathId":2134}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"IWZIUQVIZQCEDY","smiles":"[O-][N+]1=CN=C(NC2=CC=C(F)C(Cl)=C2)C2=C1C=C(OCCCCl)C(NC(=O)C=C)=C2","intrinsicScore":0.024,"id":40,"pathId":2134}],"RXN":"C=CCC(=O)Cl.c1cc(c(cc1Nc2c3cc(c(cc3[n+](cn2)[O-])OCCCCl)N)Cl)F>>C=CC(=O)Nc1cc2c(cc1OCCCCl)[n+](cnc2Nc3ccc(c(c3)Cl)F)[O-];0.0;Unrecognized"},{"depth":2,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.024,"id":9,"pathId":2134}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UJQLQQNIAMXKKN","smiles":"[O-][N+]1=C2C=C(OCCCN3CCOCC3)C(NC(=O)C=C)=CC2=C(NC2=CC(Cl)=C(F)C=C2)N=C1","intrinsicScore":0.24,"id":16,"pathId":2134}],"RXN":"[CH2:13]=[CH:12][C:11](=[O:14])[NH:10][c:9]1[cH:8][c:7]2[c:6]([cH:20][c:15]1[O:16][CH2:17][CH2:18][CH2:19]Cl)[n+:4]([cH:3][n:2][c:1]2[NH:21][c:22]3[cH:23][cH:24][c:25]([c:26]([cH:28]3)[Cl:27])[F:29])[O-:5].[CH2:32]1[CH2:31][O:30][CH2:35][CH2:34][NH:33]1>>[CH2:13]=[CH:12][C:11](=[O:14])[NH:10][c:9]1[cH:8][c:7]2[c:6]([cH:20][c:15]1[O:16][CH2:17][CH2:18][CH2:19][N:33]3[CH2:32][CH2:31][O:30][CH2:35][CH2:34]3)[n+:4]([cH:3][n:2][c:1]2[NH:21][c:22]4[cH:23][cH:24][c:25]([c:26]([cH:28]4)[Cl:27])[F:29])[O-:5];1.6.4;Chloro"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":2134}],"RXN":"C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)[n+](cnc2Nc4ccc(c(c4)Cl)F)[O-]>C1CCOC1.CCO.O.[Cl-].[Fe].[NH4+]>C=CC(=O)Nc1cc2c(cc1OCCCN3CCOCC3)ncnc2Nc4ccc(c(c4)Cl)F;0.0;Unrecognized"},{"pathScore":"-8.67","depth":0,"reaction":{"label":">>0","id":0,"pathId":714},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.011603832244873047,\"rxn_id\":\"ord-4867f59f2cd54d4b9726e8e2bbbc8d95\",\"index\":502169,\"rxn_smiles\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"procedure_details\":\"To a cold (−10° C.) solution of 3-bromo-4-(2-chloro-5-fluorophenoxy)pyridine (1.98 g, 6.54 mmol) in conc. sulfuric acid (5 ml) was added nitric acid (0.55 ml, 8.69 mmol). The resultant mixture was stirred at the same temp for 20 minutes and was then allowed to warm to ambient temp for 30 min. The reaction mixture was treated with crushed ice, stirred, filtered, washed and dried to provide 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine, (2.08 g, 91% yield) as orange yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.62 (m, 2H), 7.81 (d, J=8 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H); MS (ESI) m\\/z: 348.9 (M+1H+).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(Cl)c(Oc2ccncc2Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.988396167755127,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Cl:16].[N+:17]([O-])([OH:19])=[O:18]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:17]([O-:19])=[O:18])=[CH:11][C:10]=1[Cl:16]\",\"yield_000\":91.5},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01730966567993164,\"rxn_id\":\"ord-74806604cd9e4fe8b3ef53597a808a4c\",\"index\":656917,\"rxn_smiles\":\"Fc1ccc(OC(F)(F)F)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"procedure_details\":\"At −10° C., 90% fuming nitric acid (25 mL) was added to concentrate sulfuric acid (50 mL) slowly to keep the temperature below 0° C. At −20° C., 1-fluoro-4-trifluoromethoxy-benzene (5 g, 27.7 mmol) was added portionwise to keep the temperature of the reaction mixture below 0° C. After addition, the reaction mixture was kept at 0° C. for 30 min, poured into ice-water, extracted with EtOAc. The extracts were concentrated to give a mixture (6.05 g) of 4-fluoro-2-nitro-1-trifluoromethoxy-benzene and 1-fluoro-2-nitro-4-trifluoromethoxy-benzene in a 3:1 ratio. The crude nitration product (6.05 g) was dissolved in ethanol (40 mL) and shacked with 10% Pd\\/C (310 mg) and concentrate HCl (2.8 mL) under H2 (50 psi) for 3.5 h. Filtration and concentration gave a mixture (8.0 g) of 5-fluoro-2-trifluoromethoxy-phenylamine and its isomer 2-fluoro-5-trifluoromethoxy-phenylamine in 3:1 ratio. Without purification, the phenylamines (7 g, 35.8 mmol) were suspended in dichloromethane (100 mL), treated with trifluoroacetic anhydride (71 mmol) and triethylamine (20 mL) for 16 h. The reaction mixture was washed with saturated NaHCO3 and brine. The organic phase was further purified by silica gel chromatography (hexane\\/EtOAc 9:1) to give a mixture (5.29 g) of 2,2,2-trifluoro-N-(5-fluoro-2-trifluoromethoxy-phenyl)-acetamide and its isomer in 1:4 ratio, which was nitrated in a same procedure as the first step. The nitrate (3 g) was heated under reflux with morpholine (10 mL) in 1,2-dichloroethane (30 mL) for 3 h. Evaporation to remove excess morpholine. The residue was diluted with dichloromethane, washed with HCl (0.5N, 100 mL). The organic phase was purified by FC (hexane\\/EtOAc 7:3 to 1:1) to give the title compound 5-morpholin-4-yl-4-nitro-2-trifluoromethoxy-phenylamine (2.48 g). LC-MS: m\\/e=306.1 (M−H), 308.2 (M+H). 1H-NMR (500 MHz, CDCl3): 8.04 (s, 1H), 6.35 (s, 1H), 4.54 (br. s, 1H), 3.90 (t, 4H), 3.07 (t, 4H).\",\"reactant_000\":\"Fc1ccc(OC(F)(F)F)cc1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9826903343200684,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(F)ccc1OC(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1>>[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]([F:14])([F:15])[F:16])=[C:10]([N+:1]([O-:4])=[O:2])[CH:11]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01734292507171631,\"rxn_id\":\"ord-dc665527b3884235bf2d1dcfd379d226\",\"index\":711676,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)cc1Cl.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"procedure_details\":\"About 500 parts of aqueous nitric acid was added slowly, with stirring, to a reaction vessel containing about 400 parts of 3-chloro-4-fluorobenzotrifluoride. The temperature of the reaction mixture was maintained at about 40° C. during the addition, then raised to about 60° C. and maintained thereat for about 5 hours. The reaction mixture was allowed to settle. The aqueous layer was removed and the organic layer was washed twice with 500 parts of water, treated several times with a saturated solution of sodium bicarbonate, washed with water again, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled at reduced pressure to yield 347 parts of 5-chloro-4-fluoro-2-nitrobenzotrifluoride.\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)cc1Cl\",\"rxn_time\":5.0,\"reactant_003\":null,\"similarity\":0.9826570749282837,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":40.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1C(F)(F)F\",\"rxn_str\":\"[N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:10][C:11]=1[F:12]>>[Cl:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([N+:1]([O-:4])=[O:2])=[C:8]([C:13]([F:14])([F:15])[F:16])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.01819521188735962,\"rxn_id\":\"ord-722135299d044379bf2a69df7d4c9289\",\"index\":599739,\"rxn_smiles\":\"Fc1ccc(F)c(Cl)c1.O=S(=O)(O)O.O=[N+]([O-])O>>O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"procedure_details\":\"1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mol) was dissolved in sulfuric acid (110 ml) at −40° C., then a solution of sulfuric acid (20 ml) and nitric acid (30 ml) was added dropwise. The mixture was stirred for 1 hr while temperature slowly raised to 20° C. The product was forced to crystallize by mixing the reaction mixture with ice-water (500 ml), the yellow crystals were filtered, washed with cold water and dried in fume hood overnight. (38.0 g). 1H NMR (CDCl3, 300 MHz) 7.46 (1H, dd, J=9.8, 9.9 Hz), 7.96 (1H, dd, J=7.9, 7.9 Hz) ppm.\",\"reactant_000\":\"Fc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9818047881126404,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Cl)cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([F:8])[CH:7]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018996834754943848,\"rxn_id\":\"ord-54338fddabe442829f6eed0f79d5bb8b\",\"index\":579007,\"rxn_smiles\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"procedure_details\":\"A 1.1 g (3.85 mmol) sample of 3-chloro-2-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine was added to 8.0 ml of a 1:1 mixture of concentrated sulfuric\\/nitric acid at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes followed by warming to 20° C. After pouring the reaction mixture onto ice\\/water, the resulting aqueous mixture was extracted with 400 ml of ethyl acetate. The separated organic layer was washed with water, brine, and dried over magnesium sulfate. The yellow oily solid residue obtained after evaporating in vacuo was flash chromatographed on silica gel (1:1 hexane\\/ethyl acetate) to provide 0.8 g of the title compound as a yellow solid (m.p. 111°-112° C.). NMR (CDCl3, 200 MHz): δ1.95 (m, 2H), 2.05 (m, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 7.66 (s, 1H), 8.09 (s, 1H).\",\"reactant_000\":\"O=[N+]([O-])O\",\"reactant_002\":null,\"reactant_001\":\"Clc1ccc(-c2nc3n(c2Cl)CCCC3)c(Cl)c1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9810031652450562,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(-c2nc3n(c2Cl)CCCC3)c(Cl)cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18].[N+:19]([O-])([OH:21])=[O:20]>>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18]\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":null,\"distance\":0.002307116985321045,\"rxn_id\":\"ord-1f2a37b24b834064aa176ef473e52b7b\",\"index\":708713,\"rxn_smiles\":\"CCC(C)O.COC(=O)c1ccc2c(Cl)ncnc2c1.Nc1ccc(OC(F)(F)F)cc1>>COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"procedure_details\":\"To a solution of methyl 4-chloroquinazoline-7-carboxylate (610 mg, 2.75 mmol) in sec-BuOH (5 mL) was added 4-trifluoromethoxyaniline (535.5 mg, 3.02 mmol) at room temperature. The mixture was heated at 100° C. and stirred for 2 h. The solvent was evaporated and the compound was crystallized from CHCl3 and Et2O mixture (3:1). The white crystals were collected by filtration and washed with Et2O. (890 mg, 91% Yield). MS m\\/z 364.10 (M+1).\",\"reactant_000\":\"COC(=O)c1ccc2c(Cl)ncnc2c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(OC(F)(F)F)cc1\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.997692883014679,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"COC(=O)c1ccc2c(Nc3ccc(OC(F)(F)F)cc3)ncnc2c1\",\"rxn_str\":\"Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>C(O)(CC)C>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1\",\"yield_000\":91.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0026649832725524902,\"rxn_id\":\"ord-ceaa673ed9114e78a012af90b9ce2e3d\",\"index\":237133,\"rxn_smiles\":\"CC(C)O.COCCOc1ccc2c(Cl)ncnc2c1.Cl.Nc1ccc(Cl)cc1F>>COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"procedure_details\":\"A solution of 4-chloro-7-(2-methoxyethoxy)quinazoline hydrochloride (624 mg, 2.27 mmol) and 4-chloro-2-fluoroaniline (305 μl, 2.6 mmol) in isopropanol (20 ml) was heated at reflux for 30 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium hydrogen carbonate solution, then with water, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazoline (662 mg, 84%) as a white solid.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"COCCOc1ccc2c(Cl)ncnc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973350167274475,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COCCOc1ccc2c(Nc3ccc(Cl)cc3F)ncnc2c1\",\"rxn_str\":\"Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C(O)(C)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:21]([F:26])[CH:20]=1\",\"yield_000\":83.9},{\"solvent_000\":\"C1COCCO1\",\"solvent_001\":\"CC(C)O\",\"distance\":0.0037288665771484375,\"rxn_id\":\"ord-19694bcb96cb47fc97ac954b05ee04b2\",\"index\":638182,\"rxn_smiles\":\"C1COCCO1.CC(C)O.Cl.Fc1cc(F)c2c(Cl)ncnc2c1.Nc1ccc(F)c(Cl)c1>>Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"procedure_details\":\"3-Chloro-4-fluoroaniline (12 g) and 1N HCl in dioxane (40 ml) were added sequentially, each in one portion, to a mixture of 4-chloro-5,7-difluoroquinazoline (16.5 g) in IPA (250 ml) and the mixture was stirred at 80° C. under a nitrogen atmosphere for 17 hours. The reaction mixture was cooled to 0° C. and the precipitated solid was filtered and dried to leave N-(3-chloro-4-fluorophenyl)-5,7-difluoroquinazolin-4-amine as a green solid (18.2 g, 71%); Mass spectrum MH+ 310.\",\"reactant_000\":\"Nc1ccc(F)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"Fc1cc(F)c2c(Cl)ncnc2c1\",\"rxn_time\":17.0,\"reactant_003\":null,\"similarity\":0.9962711334228516,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"Fc1cc(F)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[CH:14][N:13]=1>O1CCOCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[CH:14][N:13]=2)[CH:6]=[CH:7][C:8]=1[F:9]\",\"yield_000\":71.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004036307334899902,\"rxn_id\":\"ord-4ecdb397e82741508819fd730ee6c9cd\",\"index\":666502,\"rxn_smiles\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1.Nc1ccc(OCc2ccccc2)cc1>>Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"procedure_details\":\"The title compound was prepared according to Procedure A from 4-benzyloxyaniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidine; δH [2H6]DMSO 11.33 (1H,s), 9.49 (1H,s), 9.39 (1H,s), 8.93 (1H,s), 7.80 (2H,d), 7.53 (2H,dd), 7.45 (3H,m), 7.20 (2H,d), 5.25 (2H,s), 2.75 (3H,s); m\\/z (M+1+) 411.\",\"reactant_000\":\"Nc1ccc(OCc2ccccc2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1nnc(-c2cc3c(Cl)ncnc3cn2)o1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959636926651001,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1nnc(-c2cc3c(Nc4ccc(OCc5ccccc5)cc4)ncnc3cn2)o1\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH:26]=[C:25]([C:27]3[O:28][C:29]([CH3:32])=[N:30][N:31]=3)[N:24]=[CH:23][C:19]=2[N:20]=[CH:21][N:22]=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:18]3[CH:26]=[C:25]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.004039764404296875,\"rxn_id\":\"ord-682148ab04074f8f8c9110a87c2dbce7\",\"index\":276577,\"rxn_smiles\":\"CC(C)O.COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl.Nc1ccc(Cl)cc1F>>COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1.Cl\",\"procedure_details\":\"A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (1.2 g, 3.6 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (444 μl, 4 mmol) in isopropanol (40 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool, the precipitate was collected by filtration, washed with isopropanol then ether and dried under vacuum to give 7-benzyloxy4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 71%).\",\"reactant_000\":\"COc1cc2c(Cl)ncnc2cc1OCc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(Cl)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9959602355957031,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1\",\"rxn_str\":\"Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1>C(O)(C)C>[ClH:20].[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][C:26]=3[F:31])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1\",\"yield_000\":70.3}]","literatureScore":1,"label":"UA ALL>>468","id":468},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.68,"id":831,"pathId":714}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.046,"id":19,"pathId":714}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"WYYDIASYJLKNKP","smiles":"FC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1","intrinsicScore":0.058,"id":468,"pathId":714}],"RXN":"[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH2:12])[Cl:20])[F:19].[cH:4]1[cH:3][c:2]2[c:7]([cH:6][c:5]1[F:11])[n:8][cH:9][n:10][c:1]2Cl>>[cH:18]1[cH:17][c:16]([c:15]([cH:14][c:13]1[NH:12][c:1]2[c:2]3[cH:3][cH:4][c:5]([cH:6][c:7]3[n:8][cH:9][n:10]2)[F:11])[Cl:20])[F:19];1.3.7;Chloro"},{"depth":6,"reaction":{"label":"AT UA ALL>>469","id":469},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GRYLNZFGIOXLOG","smiles":"O[N+]([O-])=O","intrinsicScore":0.058,"id":469,"pathId":714}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":714}],"RXN":"[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][cH:16][c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[Cl:10])[F:8].[N+:2](=[O:3])(O)[O-:1]>>[cH:5]1[cH:6][c:7]([c:9]([cH:11][c:4]1[NH:12][c:13]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:19]3[n:20][cH:21][n:22]2)[F:23])[N+:2](=[O:3])[O-:1])[Cl:10])[F:8];10.2.1;Nitration"},{"depth":5,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":714}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":714}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":714}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":714}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":714}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":714}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":714}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":714}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.699","depth":0,"reaction":{"label":">>0","id":0,"pathId":974},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005404233932495117,\"rxn_id\":\"ord-76225eb83f1d49a69b3350dfc5ea5286\",\"index\":160606,\"rxn_smiles\":\"COc1cc(-c2nc3ccc(O)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC.ClCCCN1CCCCC1>>COc1cc(-c2nc3ccc(OCCCN4CCCCC4)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC\",\"procedure_details\":\"The title compound was prepared by reacting the compound of Example 104 with 3-(piperidin-1-yl)propyl chloride essentially as previously described mp 138° C., IR, NMR, MS. 584\",\"reactant_000\":\"ClCCCN1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(-c2nc3ccc(O)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945957660675049,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(-c2nc3ccc(OCCCN4CCCCC4)cc3n2Cc2ccccc2C(F)(F)F)cc(OC)c1OC\",\"rxn_str\":\"[F:1][C:2]([F:33])([F:32])[C:3]1[CH:31]=[CH:30][CH:29]=[CH:28][C:4]=1[CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([OH:15])[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=1.[N:34]1([CH2:40][CH2:41][CH2:42]Cl)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:31]=[CH:30][CH:29]=[CH:28][C:4]=1[CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([O:15][CH2:42][CH2:41][CH2:40][N:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C:16]1[CH:17]=[C:18]([O:26][CH3:27])[C:19]([O:24][CH3:25])=[C:20]([O:22][CH3:23])[CH:21]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.0063250064849853516,\"rxn_id\":\"ord-3166dd898c594256b3d4f5254941b7f6\",\"index\":764054,\"rxn_smiles\":\"CN(C)C=O.ClCCCN1CCCC1.O=C1NCCc2ccc(O)cc21>>O=C1NCCc2ccc(OCCCN3CCCC3)cc21\",\"procedure_details\":\"7-(3-Pyrrolidin-1-yl-propoxy)-3,4-dihydro-2H-isoquinolin-1-one is prepared from 7-hydroxy-3,4-dihydro-2H-isoquinolin-1-one (0.48 g, 2.94 mmol) in a manner substantially analogous to Procedure A except DMF is used in place of dioxane and 1-(3-Chloro-propyl)-pyrrolidine is used instead of N-(3-chloropropyl)piperidine. Following aqueous workup, the crude material is purified by flash chromatography (Biotage 40M SiO2, elute 90\\/10\\/1 CH2Cl2\\/MeOH\\/NH4OH) to give the title compound as an off-white solid (0.17 g, 21%). MS (ES+) 275.1\",\"reactant_000\":\"ClCCCN1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"O=C1NCCc2ccc(O)cc21\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9936749935150146,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCc2ccc(OCCCN3CCCC3)cc21\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.Cl[CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1>CN(C=O)C>[N:17]1([CH2:16][CH2:15][CH2:14][O:1][C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][NH:8][C:9]3=[O:12])=[CH:4][CH:3]=2)[CH2:21][CH2:20][CH2:19][CH2:18]1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"O\",\"distance\":0.0064890384674072266,\"rxn_id\":\"ord-a4995629b6204d468d5b4336e14f9897\",\"index\":449830,\"rxn_smiles\":\"CC(C)O.COc1cc2oc(=O)c(C)c(C)c2cc1O.Cl.ClCCCN1CCN(Cc2ccc(Cl)cc2)CC1.O>>COc1cc2oc(=O)c(C)c(C)c2cc1OCCCN1CCN(Cc2ccc(Cl)cc2)CC1\",\"procedure_details\":\"Method D (5 h at 90° C.); starting materials: 6-hydroxy-7-methoxy-3,4-dimethyl-2H-1-benzopyran-2-one (example 103) and 1-[(4-chlorophenyl)methyl]-4-(3-chloropropyl)piperazine; yield: 74%; fusion point 96°-97° C. (from isopropanol and petroleum ether). Hydrochloride (x 2 HCl): method G; yield 95%; fusion point 255°-260° C. (from isopropanol and water).\",\"reactant_000\":\"COc1cc2oc(=O)c(C)c(C)c2cc1O\",\"reactant_002\":null,\"reactant_001\":\"ClCCCN1CCN(Cc2ccc(Cl)cc2)CC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9935109615325928,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2oc(=O)c(C)c(C)c2cc1OCCCN1CCN(Cc2ccc(Cl)cc2)CC1\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([O:15][CH3:16])=[CH:4][C:5]2[O:10][C:9](=[O:11])[C:8]([CH3:12])=[C:7]([CH3:13])[C:6]=2[CH:14]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:25]2[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][CH2:33]Cl)[CH2:27][CH2:26]2)=[CH:20][CH:19]=1.C(O)(C)C.Cl>O>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:24][N:25]2[CH2:26][CH2:27][N:28]([CH2:31][CH2:32][CH2:33][O:1][C:2]3[C:3]([O:15][CH3:16])=[CH:4][C:5]4[O:10][C:9](=[O:11])[C:8]([CH3:12])=[C:7]([CH3:13])[C:6]=4[CH:14]=3)[CH2:29][CH2:30]2)=[CH:22][CH:23]=1\",\"yield_000\":74.0},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.006968259811401367,\"rxn_id\":\"ord-f52c27df0db34e649570e622c832e52b\",\"index\":481109,\"rxn_smiles\":\"CC(C)O.Cl.ClCCCN1CCOCC1.O=c1oc2ccccc2c(O)c1-c1ccccc1>>O=c1oc2ccccc2c(OCCCN2CCOCC2)c1-c1ccccc1\",\"procedure_details\":\"This compound is obtained by the method indicated in Example 8, from 14.3 g. (0.06 mol) of 4-hydroxy-3-phenyl-coumarin and 15.6 g. (0.078 mol) of 3-morpholino-1-chloropropane hydrochloride. 15.6 g. of a white solid are isolated. Yield 71% (theoretical yield 21.9 g.); M.P. 82° C. (isopropanol).\",\"reactant_000\":\"O=c1oc2ccccc2c(O)c1-c1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCN1CCOCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9930317401885986,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=c1oc2ccccc2c(OCCCN2CCOCC2)c1-c1ccccc1\",\"rxn_str\":\"[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][C:4](=[O:12])[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl.[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28]Cl)[CH2:22][CH2:21]1>C(O)(C)C>[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][O:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[O:5][C:4](=[O:12])[C:3]=2[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:22][CH2:21]1\",\"yield_000\":71.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.007157027721405029,\"rxn_id\":\"ord-52e5908a3e544508ac862e3188228f8e\",\"index\":355561,\"rxn_smiles\":\"ClCCCN1CCCC1.N#CCc1ccccc1O>>N#CCc1ccccc1OCCCN1CCCC1\",\"procedure_details\":\"The title compound was prepared from 2-hydroxy-benzeneacetonitrile (J. Org. Chem.; 66, 3435; 2001) and 1-(3-chloropropyl)pyrrolidine, using a method similar to that of preparation 104, as a pale brown gum in 58% yield. 1H NMR (400 MHz, CD3OD) δ: 7.33-7.25 (2H, m), 7.02-6.90 (2H, m), 4.12-4.09 (2H, m), 3.75 (2H, s), 2.76-2.72 (2H, m), 2.62-2.57 (4H, m), 2.09-2.02 (2H, m), 1.87-1.78 (4H, m); LRMS APCI m\\/z 245 [M+H]+\",\"reactant_000\":\"ClCCCN1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"N#CCc1ccccc1O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992842972278595,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#CCc1ccccc1OCCCN1CCCC1\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]#[N:10].Cl[CH2:12][CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1>>[N:15]1([CH2:14][CH2:13][CH2:12][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:8][C:9]#[N:10])[CH2:19][CH2:18][CH2:17][CH2:16]1\",\"yield_000\":58.0}]","literatureScore":0.99,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002769649028778076,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9972303509712219,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0031270384788513184,\"rxn_id\":\"ord-dcc1a5efa86d4d09b08ec14f86ec1748\",\"index\":264188,\"rxn_smiles\":\"Cl.O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12>>Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"procedure_details\":\"A solution of stannous chloride dihydrate (3.7 g, 16 mmol) in 10 ml of conc. hydrochloric acid was added dropwise to a stirred suspension of 2,3-dihydroxy-6-nitrobenzo(f)quinoxaline (1.3 g, 5 mmol) in 8 ml of conc. hydrochloric acid. Then the mixture was stirred at 60-70° C. on an oil bath for 2 h. After cooling on ice, the precipitate was collected, dissolved in boiling water (1 1), filtered while hot, and neutralized to pH 6 with solid sodium hydrogen carbonate. The yellow product was isolated and recrystallized from DMF\\/water, washed with water, ethanol and ether and finally dried at 110 ° C. to give 0.90 g (63%) of pure title compound, m.p. >300° C., IR (KBr): 1690, ? 1640 and 1605 cm-1,1H-NMR (DMSO-d6): 5.8 (broad s, 2H,NH2), 6.63(s,1H, H-5), 7.2-8.7 (m, 4H, ArH), 11.8 (broad s, 2H, 20H).\",\"reactant_000\":\"O=[N+]([O-])c1cc2nc(O)c(O)nc2c2ccccc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9968729615211487,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":65.0,\"product_000\":\"Nc1cc2nc(O)c(O)nc2c2ccccc12\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([OH:19])=[N:4][C:5]2[CH:6]=[C:7]([N+:16]([O-])=O)[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[N:11]=1>Cl>[NH2:16][C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]2[N:11]=[C:2]([OH:1])[C:3]([OH:19])=[N:4][C:5]=2[CH:6]=1\",\"yield_000\":79.2},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.00328141450881958,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9967185854911804,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003656148910522461,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963438510894775,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003899812698364258,\"rxn_id\":\"ord-fc93af0f0d9a40e284c2500298acaf93\",\"index\":573049,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"The crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine was dissolved in THF and reduced using Raney nickel catalyst to yield N4-(3-Chloro-4-fluoro-phenyl)-7-(2,2-difluoro-ethoxy)-quinazoline-4,6-diamine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961001873016357,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C1COCC1.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]([F:27])[F:26])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null}]","literatureScore":1,"label":"UA CF T5 AT ER TTL ALL>>33","id":33},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":974}]},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":974}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":974}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":974}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.68,"id":154,"pathId":974}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEFNIUDZICAGOU","smiles":"NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1O","intrinsicScore":0.051,"id":33,"pathId":974}],"RXN":"[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[N+:21](=O)[O-])[Cl:18])[F:20]>>[cH:14]1[cH:15][c:16]([c:17]([cH:19][c:13]1[NH:12][c:11]2[c:3]3[cH:2][c:1]([c:6]([cH:5][c:4]3[n:8][cH:9][n:10]2)[OH:7])[NH2:21])[Cl:18])[F:20];7.1.1;Nitro"},{"depth":3,"reaction":{"label":"AT T5 ER UA TTL ALL>>13","id":13},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"PIAZYBLGBSMNLX","smiles":"ClCCCN1CCOCC1","intrinsicScore":0.051,"id":13,"pathId":974}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":974}],"RXN":"[cH:4]1[cH:3][c:2]([c:1]([cH:6][c:5]1[NH:7][c:8]2[c:9]3[cH:19][c:17]([c:15]([cH:14][c:10]3[n:11][cH:12][n:13]2)[OH:16])[NH2:18])[Cl:21])[F:20].[CH2:22]1[CH2:27][O:26][CH2:25][CH2:24][N:23]1[CH2:28][CH2:29][CH2:30]Cl>>[cH:4]1[cH:3][c:2]([c:1]([cH:6][c:5]1[NH:7][c:8]2[c:9]3[cH:19][c:17]([c:15]([cH:14][c:10]3[n:11][cH:12][n:13]2)[O:16][CH2:30][CH2:29][CH2:28][N:23]4[CH2:22][CH2:27][O:26][CH2:25][CH2:24]4)[NH2:18])[Cl:21])[F:20];1.7.9;Williamson"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":974}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":974}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":974}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.709","depth":0,"reaction":{"label":">>0","id":0,"pathId":169},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.6,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.008023500442504883,\"rxn_id\":\"ord-42dc5bd007e148f297483fd574a84112\",\"index\":514864,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCN(CC)CC.Cl.Cl.N#Cc1ccc(Cn2cncc2CCN)cc1F>>N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride (0.92 g, 0.0029 mmol) in acetonitrile (150 mL) and triethylamine (3.2 mL) was added 2-bromoethyl ether (0.839 mL, 0.0067 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in uacuo and the residue was dissolved in EtOAc which was washed twice with 1M HCl (100 mL). The HCl layers were combined and adjusted to pH=9 with solid Na2CO3 and extraxcted 3 times with EtOAc. The EtOAc layers were combined and dried with brine and MgSO4. Removal of the EtOAc in vacuo yielded the title compound which was used as is in the next step.\",\"reactant_000\":\"N#Cc1ccc(Cn2cncc2CCN)cc1F\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919764995574951,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(Cn2cncc2CCN2CCOCC2)cc1F\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=2)[CH:9]=[N:8][CH:7]=1.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>C(#N)C.C(N(CC)CC)C>[F:20][C:14]1[CH:13]=[C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][N:3]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:7][N:8]=[CH:9]2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.008291244506835938,\"rxn_id\":\"ord-08bb54aa0ab244ff90317c31f9d4c5e8\",\"index\":731783,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.NC1CCN(Cc2ccccc2)CC1.O=C([O-])[O-].[K+].[K+]>>c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"procedure_details\":\"To a stirred mixture of 4-amino-1-benzylpiperidine (1.53 mL, 7.5 mmol), K2CO3 (2.28 g, 16.5 mmol) and DMF (15 mL) heated at 50° C. was added dropwise over 60 min bis(2-bromoethyl) ether (0.96 mL, 7.65 mmol). After stirring for 6 hours at 80° C., the solvent was removed by blowing with a stream of nitrogen over 2 hours. The residue was purified on a silica gel column to give 1.7 g (87%) of 4-(1-benzyl-piperidin-4-yl)morpholine as a waxy solid.\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"NC1CCN(Cc2ccccc2)CC1\",\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9917087554931641,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"c1ccc(CN2CCC(N3CCOCC3)CC2)cc1\",\"rxn_str\":\"[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br>CN(C=O)C>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:1]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1\",\"yield_000\":87.1},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.008305191993713379,\"rxn_id\":\"ord-ac7a693c46694fd5b13039f5c104d79e\",\"index\":134482,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N.O=C([O-])[O-].[K+].[K+]>>CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"procedure_details\":\"cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane\\/methanol\\/ammonia 100:0:0->140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m\\/e=403.3 [(M+H)+].\",\"reactant_000\":\"BrCCOCCBr\",\"reactant_002\":null,\"reactant_001\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9916948080062866,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1\",\"rxn_str\":\"[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]\",\"yield_000\":68.6},{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CC#N\",\"distance\":0.00859677791595459,\"rxn_id\":\"ord-aa3eb88c8e6c445794e16d41429514f0\",\"index\":719114,\"rxn_smiles\":\"BrCCOCCBr.CC#N.CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O.CCN(CC)CC.Cl.Cl>>CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"procedure_details\":\"To a solution of 4-[5-(2-amino-ethyl)-2-methyl-imidazol-1-ylmethyl]-2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile dihydrochloride (as described in Example 11) (0.25 g, 0.456 mmol) in acetonitrile (35.0 mL) and triethylamine (1.8 mL) was added 2-bromoethyl ether (0.133 mL, 1.06 mmol) and the mixture was refluxed for 48 hr. The solvents were removed in vacuo to obtain the title compound after purification by preparative HPLC.\",\"reactant_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9914032220840454,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCC1(c2cccc(Oc3cc(Cn4c(CCN5CCOCC5)cnc4C)ccc3C#N)c2)CCCCN(C)C1=O\",\"rxn_str\":\"Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]4([CH2:36][CH3:37])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]4=[O:35])[CH:22]=3)[CH:13]=2)[C:9]([CH3:38])=[N:8][CH:7]=1.Br[CH2:40][CH2:41][O:42][CH2:43][CH2:44]Br>C(#N)C.C(N(CC)CC)C>[CH2:36]([C:27]1([C:23]2[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=2)[O:20][C:14]2[CH:13]=[C:12]([CH2:11][N:10]3[C:6]([CH2:5][CH2:4][N:3]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[CH:7][N:8]=[C:9]3[CH3:38])[CH:19]=[CH:18][C:15]=2[C:16]#[N:17])[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[C:28]1=[O:35])[CH3:37]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.008690357208251953,\"rxn_id\":\"ord-90e436a959164d40ab8c094946564425\",\"index\":740936,\"rxn_smiles\":\"BrCCOCCBr.CN(C)C=O.Nc1ccc(Br)c(Cl)c1.O.O=C([O-])[O-].[I-].[K+].[K+].[K+]>>Clc1cc(N2CCOCC2)ccc1Br\",\"procedure_details\":\"4-Bromo-3-chloroaniline (500 mg) was dissolved in DMF (10 ml), and bis(2-bromoethyl)ether (1.12 g), K2CO3 (1.34 g), and potassium iodide (80 mg) were added thereto, followed by stirring at 80° C. for 2 days. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 20% EtOAc\\/hexane) to obtain 4-(4-bromo-3-chlorophenyl)morpholine (263 mg).\",\"reactant_000\":\"Nc1ccc(Br)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":\"BrCCOCCBr\",\"rxn_time\":48.0,\"reactant_003\":null,\"similarity\":0.991309642791748,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[I-]\",\"agent_002\":\"[K+]\",\"temperature\":80.0,\"product_000\":\"Clc1cc(N2CCOCC2)ccc1Br\",\"rxn_str\":\"[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:9].Br[CH2:11][CH2:12][O:13][CH2:14][CH2:15]Br.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][C:3]=1[Cl:9]\",\"yield_000\":39.3}]","literatureScore":0.99,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":3.3,"literature":"[{\"solvent_000\":\"c1ccncc1\",\"solvent_001\":\"CCO\",\"distance\":0.0034121274948120117,\"rxn_id\":\"ord-c978110d0ebb47c5ab077decdb013eb8\",\"index\":750238,\"rxn_smiles\":\"CCO.CP(C)C.[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1.[NH4+].[OH-].c1ccncc1>>NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"procedure_details\":\"To a solution of (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 0.230 mmol) in pyridine (2 mL) was added NH4OH (200 μl) and trimethylphosphine (344 μl, 0.344 mmol) sequentially at room temperature. The reaction mixture was stirred for 2 h. After EtOH (1 mL) was added, the reaction mixture was concentrated in vacuo. The crude product was purified by flash chromatography (20% MeOH in DCM containing 0.5% NH3\\/DCM) to provide 89.6 mg of (S)\\u2014N-(2-amino-1-(3-chloro-5-fluorophenyl)ethyl)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamide (79%). LCMS (m\\/z): 488.2 (MH+), 0.66 min. 1H NMR (500 MHz, METHANOL-d4) δ ppm 7.98-7.89 (m, 1H), 7.89-7.79 (m, 1H), 7.74 (td, J=1.4, 8.0 Hz, 1H), 7.69-7.61 (m, 1H), 7.41-7.28 (m, 1H), 7.27-7.08 (m, 2H), 5.27-5.12 (m, 1H), 4.07 (dd, J=3.8, 11.0 Hz, 2H), 3.69-3.52 (m, 2H), 3.14-3.03 (m, 2H), 2.96 (tt, J=3.9, 11.7 Hz, 1H), 2.02-1.77 (m, 4H).\",\"reactant_000\":\"[N-]=[N+]=NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996587872505188,\"agent_000\":\"CP(C)C\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"NC[C@@H](NC(=O)c1ccc(-c2nc(C3CCOCC3)cnc2N)cc1F)c1cc(F)cc(Cl)c1\",\"rxn_str\":\"[NH2:1][C:2]1[C:3]([C:14]2[CH:35]=[CH:34][C:17]([C:18]([NH:20][C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=3)[CH2:22][N:23]=[N+]=[N-])=[O:19])=[C:16]([F:36])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[NH4+].[OH-].CP(C)C.CCO>N1C=CC=CC=1>[NH2:23][CH2:22][C@@H:21]([NH:20][C:18](=[O:19])[C:17]1[CH:34]=[CH:35][C:14]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([CH:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:4]=2)=[CH:15][C:16]=1[F:36])[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([Cl:33])[CH:27]=1\",\"yield_000\":79.8},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.004088282585144043,\"rxn_id\":\"ord-042249e7216a47579d0f62148c807cd2\",\"index\":714256,\"rxn_smiles\":\"C1CCOC1.C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21>>NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"procedure_details\":\"20 μL of a 1M trimethylphosphine\\/tetrahydrofuran solution was added to 6 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-azidoethyl) ester dissolved in a mixture of 0.15 mL of tetrahydrofuran and 0.02 mL of water at room temperature, and the mixture was stirred for 13 hours. After the solvent was distilled under reduced pressure, the residue was purified by reverse phase column chromatography (Wako gel 50C18 (made by Wako Pure Chemical Industries Ltd.), eluent: water to a 50% aqueous solution of acetonitrile), and the obtained solids were further washed with tetrahydrofuran, thereby yielding 2 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-(2-aminoethyl)ester.\",\"reactant_000\":\"[N-]=[N+]=NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":13.0,\"reactant_003\":null,\"similarity\":0.995911717414856,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](OCc3ccc(Cl)c(Cl)c3)[C@@](N)(C(=O)O)[C@@H]21\",\"rxn_str\":\"CP(C)C.O1CCCC1.[N:10]([CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17])=[N+]=[N-]>O1CCCC1.O>[NH2:10][CH2:13][CH2:14][O:15][C:16]([C@:18]1([F:38])[C@@H:23]2[C@H:19]1[CH2:20][C@@H:21]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=1)[C@@:22]2([NH2:27])[C:24]([OH:26])=[O:25])=[O:17]\",\"yield_000\":35.4},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0043354034423828125,\"rxn_id\":\"ord-d978c1c7e23041a1b604dc1dd6ff7a6f\",\"index\":562746,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1>>NCc1cncc(C#Cc2ccccc2)c1\",\"procedure_details\":\"To a solution of 3-(azidomethyl)-5-(phenylethynyl)pyridine (7.8 g, 33.3 mmol) in tetrahydrofuran (101 mL) at 0° C. was added trimethylphosphine (1M in tetrahydrofuran, 49.9 mL, 49.9 mmol). After evolution of nitrogen had slowed, the ice bath was removed and stirring continued for 1 h. To this was added water (6.0 mL, 333 mmol) and the mixture stirred at room temperature for 2 h. The reaction was concentrated, dissolved in ether, washed with water (5×), then brine, dried over potassium carbonate, filtered, and concentrated to give 5.96 g (77%) as a faint yellow solid which was used without purification. 1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H)1H NMR (CDCl3) δ: 8.67 (d, J=1.8 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 7.85 (t, J=2.0 Hz, 1H), 7.53-7.61 (m, 2H), 7.35-7.44 (m, 3H), 3.95 (s, 2H), 1.45 (d, J=5.2 Hz, 2H). 13C NMR (CDCl3) δ: 150.8, 147.9, 137.8, 137.4, 131.8, 128.9, 128.6, 122.7, 120.3, 92.7, 86.1, 43.7. Mass spec.: 209.1 (MH)+.\",\"reactant_000\":\"[N-]=[N+]=NCc1cncc(C#Cc2ccccc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9956645965576172,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCc1cncc(C#Cc2ccccc2)c1\",\"rxn_str\":\"[N:1]([CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[N+]=[N-].CP(C)C.O>O1CCCC1>[C:13]1([C:12]#[C:11][C:9]2[CH:10]=[C:5]([CH2:4][NH2:1])[CH:6]=[N:7][CH:8]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1COCCO1\",\"distance\":0.005223870277404785,\"rxn_id\":\"ord-089f68b08fe543bfbdedd8c9521524ae\",\"index\":377104,\"rxn_smiles\":\"C1COCCO1.CP(C)C.O.[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21>>NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"procedure_details\":\"Azide 23 (Example 10, 100 mg, 0.23 mmol) is dissolved in 0.9 mL of 1,4-dioxane\\/H2O (8:1), and 0.3 mL of a trimethylphospine solution (1 M in THF) is added. The reaction is stirred at room temperature for 3 h, then all volatiles are removed in vacuo. The crude product is purified by flash column chromatography with dichloromethane\\/methanol (95:5 to 10:1). Yield: 87 mg (0.021 mmol, 91%).\",\"reactant_000\":\"[N-]=[N+]=NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9947761297225952,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"NCCCn1cnc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc21\",\"rxn_str\":\"[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][N:14]=[N+]=[N-])=[C:4]([O:17][CH2:18][C:19]2[CH:32]=[CH:31][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)[N:3]=1.CP(C)C>O1CCOCC1.O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH2:13][NH2:14])=[C:4]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:23][NH:24][C:25](=[O:30])[C:26]([F:27])([F:29])[F:28])=[CH:31][CH:32]=2)[N:3]=1\",\"yield_000\":null},{\"solvent_000\":\"O\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.005546689033508301,\"rxn_id\":\"ord-be83b62c5d5249cf938c714d7117d666\",\"index\":193745,\"rxn_smiles\":\"C1CCOC1.CP(C)C.O.[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1>>NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"procedure_details\":\"To a solution of (S)-2-[[1-(2-azidoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid (6.28 g, 12.11 mmol) in THF (91 mL) was added a solution of trimethylphosphine in THF (48.5 mL, 48.46 mmol, 1.0M) at 0° C. It was a clear solution in the beginning and after 30 min some precipitate was formed and this mixture was stirred for overnight at which time TLC analysis of the mixture indicated the absence of starting material. Then, 10 equiv. of water (120 mmol, 2.16 mL) was added and the mixture was stirred for 2 h at room temperature. The solvent was removed under vacuum and the residue was azeotrophed two times with toluene to give a pasty material which was purified using HPLC to obtain 4.57 g (77% yield) of (S)-2-[[1-(2-aminoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid as an amorphous white solid. ES(+)-HRMS m\\/e calcd. for C24H27Cl2N3O4 (M+H)+ 492.1452, obsd. 492.1451.\",\"reactant_000\":\"[N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9944533109664917,\"agent_000\":\"CP(C)C\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1\",\"rxn_str\":\"[N:1]([CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:21][CH:20]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:23][CH:24]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1\",\"yield_000\":76.6}]","literatureScore":1,"label":"TTL ALL>>167","id":167},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008967578411102295,\"rxn_id\":\"ord-cf2e4e3955c04b01a2130e020e40723c\",\"index\":264007,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-4-fluorophenylamine (1.67 g, 4.87 mmoles) and sodium azide (0.38 g, 5.84 mmoles) in DMSO (20 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (1.44 g, 4.14 mmoles).\",\"reactant_000\":\"Nc1c(CS(=O)(=O)c2ccccc2)cc(F)cc1OCCCl\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9910324215888977,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cc(F)cc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([O:18][CH2:19][CH2:20]Cl)[C:12]=2[NH2:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>CS(C)=O.O>[N:23]([CH2:20][CH2:19][O:18][C:13]1[CH:14]=[C:15]([F:17])[CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:22])=[N+:24]=[N-:25]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CCOC(C)=O\",\"distance\":0.00959622859954834,\"rxn_id\":\"ord-693a2494d2a64d6e84f87595007867e9\",\"index\":765833,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.O=[N+]([O-])c1ccc(OCCCCl)cc1CO.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"procedure_details\":\"DMF (7.5 mL) was added to (5-(3-chloropropoxy)-2-nitrophenyl)methanol (635 mg, 0.00258 moles) and sodium azide (252 mg, 0.00387 moles) in a flask, and the resulting mixture was heated to 70° C. and stirred overnight. The reaction was diluted in ethyl acetate (100 mL) and washed twice with water (75 mL each) and once with brine (75 mL). The organic layer was dried with anhydrous magnesium sulfate, which was filtered out. The filtrate was concentrated on a rotary evaporator and dried in vacuo overnight to yield (5-(3-azidopropoxy)-2-nitrophenyl)methanol as a yellow solid (yield 88%). H NMR (400 MHz, CD2Cl2) δ 8.16 (d, J=9.1 Hz, 1H), 7.27 (d, J=2.8 Hz, 1H), 6.91 (dd, J=9.1, 2.8 Hz, 1H), 4.98 (s, 2H), 4.18 (t, J=6.0 Hz, 2H), 3.53 (t, J=6.6 Hz, 2H), 2.12-2.06 (m, 2H). 13C-NMR (100 MHz, CD2Cl2) δ 163.99, 141.22, 128.43, 114.97, 113.93, 66.15, 63.26, 48.68, 29.13 HRMS m\\/z: calculated for C10H12N4O4 [M+H]+, 253.0931. found, 253.0939.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCCCCl)cc1CO\",\"reactant_002\":null,\"reactant_001\":\"[N-]=[N+]=[N-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9904037714004517,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"[N-]=[N+]=NCCCOc1ccc([N+](=O)[O-])c(CO)c1\",\"rxn_str\":\"CN(C=O)C.Cl[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>C(OCC)(=O)C>[N:22]([CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:19]([O-:21])=[O:20])=[C:15]([CH2:17][OH:18])[CH:16]=1)=[N+:23]=[N-:24]\",\"yield_000\":88.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CS(C)=O\",\"distance\":0.009707868099212646,\"rxn_id\":\"ord-ed6541dc83464b24a92f34950c9068d0\",\"index\":137604,\"rxn_smiles\":\"CS(C)=O.O.O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"procedure_details\":\"A mixture of 6-(2-chloro-ethoxy)-3-(naphthalene-1-sulfonyl)-1-H-indazole (0.19 g, 0.5 mmoles) and sodium azide (0.04 g, 0.62 mmoles) in DMSO (2 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.17 g, 0.45 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"O=S(=O)(c1cccc2ccccc12)c1n[nH]c2cc(OCCCl)ccc12\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9902921319007874,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1ccc2c(S(=O)(=O)c3cccc4ccccc34)n[nH]c2c1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1.[N-:27]=[N+:28]=[N-:29].[Na+]>CS(C)=O.O>[N:27]([CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1)=[N+:28]=[N-:29]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.010035336017608643,\"rxn_id\":\"ord-dc8e8747d9b6443687f6f629e49ca7d3\",\"index\":120480,\"rxn_smiles\":\"CN(C)C=O.Nc1ncnc2c1ncn2CCCCl.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"procedure_details\":\"A mixture of 9-(3-chloropropyl)adenine and sodium azide in DMF was stirred at 80° C. for 24 hours, cooled to room temperature and filtered. The solid was washed with CH2Cl2. The solvent was removed from the combined filtrates and the residue was taken up in water with sonication. The aqueous layer was extracted with CH2Cl2. After removing the solvent, the crude product was recrystallized from ethanol to give 9-(3-azidopropyl)adenine as a white crystalline solid.\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1ncnc2c1ncn2CCCCl\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9899646639823914,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"[N-]=[N+]=NCCCn1cnc2c(N)ncnc21\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14].[N-:15]=[N+:16]=[N-:17].[Na+]>CN(C=O)C>[N:15]([CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14])=[N+:16]=[N-:17]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.010115861892700195,\"rxn_id\":\"ord-5c4de244180f41a2bbc87a484238a728\",\"index\":335449,\"rxn_smiles\":\"CS(C)=O.Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl.O.[N-]=[N+]=[N-].[Na+]>>[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"procedure_details\":\"A mixture of 2-benzenesulfonylmethyl-6-(2-chloro-ethoxy)-phenylamine (0.5 g, 1.53 mmoles) and sodium azide (0.15 g, 2.29 mmoles) in DMSO (10 mL) was stirred together in a round bottom flask under nitrogen at 90° C. for 3 hours. Reaction mixture was cooled to room temperature, diluted with water, extracted with EtOAC, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Crude compound was purified by normal phase HPLC using as eluent 40% EtOAc\\/hexane to afford the title compound as an off white solid (0.39 g, 1.17 mmoles).\",\"reactant_000\":\"[N-]=[N+]=[N-]\",\"reactant_002\":null,\"reactant_001\":\"Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9898841381072998,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"[N-]=[N+]=NCCOc1cccc(CS(=O)(=O)c2ccccc2)c1N\",\"rxn_str\":\"[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19]Cl)[C:12]=2[NH2:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>CS(C)=O.O>[N:22]([CH2:19][CH2:18][O:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH2:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:12]=1[NH2:21])=[N+:23]=[N-:24]\",\"yield_000\":null}]","literatureScore":0.99,"label":"ER UA TTL ALL>>672","id":672},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004968404769897461,\"rxn_id\":\"ord-67cd89c92ec043eaa8c192a52c6055e1\",\"index\":71209,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)c(F)c2)cc1>>N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"procedure_details\":\"The product from Example 167A and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (99% yield). 1HNMR (300 MHz, CDCl3) δ2.30 (m, 2H), 3.80 (m, 2H), 4.25 (m, 2H), 7.12-7.75 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)c(F)c2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950315952301025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)=[CH:3][C:2]=1[F:1]\",\"yield_000\":99.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005435526371002197,\"rxn_id\":\"ord-593d5907c892416383020940bf139801\",\"index\":592545,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)cc2)cc1F>>N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"procedure_details\":\"The product from Example 166B and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (98% yield). 1HNMR (300 MHz, CDCl3) δ2.25 (m, 2H), 3.80 (m, 2H), 4.20 (m, 2H), 7.00-7.65 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)cc2)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945644736289978,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([F:1])[CH:3]=2)=[CH:11][CH:12]=1\",\"yield_000\":98.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005583524703979492,\"rxn_id\":\"ord-f2089ee29c9c49d6bda509b96fde9e15\",\"index\":355059,\"rxn_smiles\":\"ClCCCBr.Cn1ncc(-c2ccc(O)cc2)cc1=O>>Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"procedure_details\":\"5-[4-(3-Chloro-propoxy)-phenyl]-2-methyl-2H-pyridazin-3-one was prepared from 5-(4-hydroxy-phenyl)-2-methyl-2H-pyridazin-3-one with 1-bromo-3-chloro-propane using the procedure described in Example 86 Step 3; Mp 90-91° C.; MS m\\/z 279 (M+H).\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"Cn1ncc(-c2ccc(O)cc2)cc1=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944164752960205,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0058318376541137695,\"rxn_id\":\"ord-0943760d2d71451cb76c1188d0d02866\",\"index\":410217,\"rxn_smiles\":\"ClCCCBr.O=C1NCCn2c1cc1cc(O)cnc12>>O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"procedure_details\":\"The title compound was synthesized in analogy to example 2, intermediate, from 7-hydroxy-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one (example 84, intermediate a) and 1-bromo-3-chloropropane, to give the desired product as a light yellow solid (80%).\",\"reactant_000\":\"O=C1NCCn2c1cc1cc(O)cnc12\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941681623458862,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"rxn_str\":\"[OH:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1\",\"yield_000\":80.0},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.006563842296600342,\"rxn_id\":\"ord-cbbf3a06c7d04efaab9b011975b2bcaf\",\"index\":118810,\"rxn_smiles\":\"CC(C)=O.ClCCCBr.O=C1CSc2cc(O)ccc2N1>>O=C1CSc2cc(OCCCCl)ccc2N1\",\"procedure_details\":\"After a mixture consisting of 7-hydroxy-3,4-dihydro-2H-1,4-benzothiazin-3-one (1.812 g, 10 mmol), 1bromo-3-chloropropane (2.362 g, 15 mmol), potassium carbate (4.146 g, 30 mmol) and acetone (40 mmol) was heated under reflux and stirring for 24 hours, insolube matter was filtered off, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel column (developer: chloroform) to purify the same, and was then recrystallized from acetone. The title compound (1.300 g) was obtained as yellow leaflets (yield: 50.4%).\",\"reactant_000\":\"O=C1CSc2cc(O)ccc2N1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9934361577033997,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CSc2cc(OCCCCl)ccc2N1\",\"rxn_str\":\"[OH:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.Br[CH2:14][CH2:15][CH2:16][Cl:17].CC(C)=O>>[Cl:17][CH2:16][CH2:15][CH2:14][O:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1\",\"yield_000\":50.4}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":7,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":8,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":169}]},{"depth":8,"reaction":{"label":"TTL 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ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":169}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.43,"id":154,"pathId":169}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":6,"reaction":{"label":"TTL ALL T5 UA ER 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ALL>>990","id":990},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"JUINSXZKUKVTMD","smiles":"N=[N+]=[N-]","intrinsicScore":0.6,"id":990,"pathId":169}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"FCEJYNJLOZLCCR","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1OCCCN=[N+]=[N-]","intrinsicScore":0.3,"id":672,"pathId":169}],"RXN":"[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4]Cl)[N+:27](=[O:28])[O-:29])[Cl:24])[F:21].[NH:3]=[N+:1]=[N-:2]>>[cH:18]1[cH:19][c:20]([c:22]([cH:23][c:17]1[NH:16][c:12]2[c:11]3[cH:25][c:26]([c:8]([cH:9][c:10]3[n:15][cH:14][n:13]2)[O:7][CH2:6][CH2:5][CH2:4][N:3]=[N+:1]=[N-:2])[N+:27](=[O:28])[O-:29])[Cl:24])[F:21];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NGGHYTSBRHGJPA","smiles":"NCCCOC1=C(C=C2C(NC3=CC=C(F)C(Cl)=C3)=NC=NC2=C1)[N+]([O-])=O","intrinsicScore":0.051,"id":167,"pathId":169}],"RXN":"[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][N:20]=[N+]=[N-])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27]>C1CCOC1.C(OCC)(C)=O.CP(C)C.O>[cH:5]1[cH:4][c:3]([c:2]([cH:26][c:6]1[NH:7][c:8]2[c:9]3[cH:10][c:11]([c:15]([cH:21][c:22]3[n:23][cH:24][n:25]2)[O:16][CH2:17][CH2:18][CH2:19][NH2:20])[N+:12](=[O:14])[O-:13])[Cl:1])[F:27];9.7.13;Azido"},{"depth":3,"reaction":{"label":"TTL ALL>>51","id":51},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"FOZVXADQAHVUSV","smiles":"BrCCOCCBr","intrinsicScore":0.051,"id":51,"pathId":169}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":169}],"RXN":"[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][NH2:8])[N+:30](=[O:31])[O-:32])[Cl:29])[F:26].[CH2:2]([CH2:1]Br)[O:3][CH2:4][CH2:5]Br>N#CC.[O-]C(=O)[O-].[I-].[K+]>[cH:23]1[cH:24][c:25]([c:27]([cH:28][c:22]1[NH:21][c:15]2[c:14]3[cH:13][c:12]([c:11]([cH:20][c:19]3[n:18][cH:17][n:16]2)[O:10][CH2:9][CH2:6][CH2:7][N:8]4[CH2:1][CH2:2][O:3][CH2:4][CH2:5]4)[N+:30](=[O:31])[O-:32])[Cl:29])[F:26];4.2.5;Morpholine"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":169}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":169}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":169}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.793","depth":0,"reaction":{"label":">>0","id":0,"pathId":42},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0011646151542663574,\"rxn_id\":\"ord-ef4f3054307f419082bcbcccca161314\",\"index\":444346,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from 8-(3-bromopropoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one and morpholine following the procedure outlined in Example 18, Step 2. 1H NMR (400 MHz, DMSO-d6, HCl salt): δ 10.58 (br, 1H), 10.44 (s, 1H), 8.94 (s, 1H), 8.77 (s, 2H), 7.93 (d, 1H), 7.09 (d, 1H), 4.82 (s, 1H), 4.02 (t, 2H), 3.98 (m, 2H), 3.93 (s, 3H), 3.76 (t, 2H), 3.46 (d, 2H), 3.33 (m, 2H), 3.10 (m, 2H), 2.22 (m, 2H); MS (ESI): 479.3.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9988353848457336,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)[nH]c2c1OCCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([O:26][CH3:27])=[CH:8][CH:9]=[C:10]2[C:15]=1[NH:14][C:13](=[O:16])[CH:12]=[C:11]2[NH:17][C:18]1[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=1[Cl:25].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[Cl:25][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:24])[C:18]=1[NH:17][C:11]1[C:10]2[C:15](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:7]([O:26][CH3:27])=[CH:8][CH:9]=2)[NH:14][C:13](=[O:16])[CH:12]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.002698183059692383,\"rxn_id\":\"ord-5463a61500a24191adb453f447212d07\",\"index\":272023,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 25) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6; HCl salt): δ 10.67 (br, 1H), 9.65 (br s, 1H), 8.82 (s, 2H), 8.01 (d, 1H), 7.22 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.93 (s, 3H), 3.92 (m, 2H), 3.76 (t, 2H), 3.42 (d, 2H), 3.20 (m, 2H), 3.05 (m, 2H), 1.97 (m, 2H), 1.74 (m, 2H); MS (ESI): 494.0.\",\"reactant_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9973018169403076,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([O:33][CH3:34])=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[CH:19]=[C:18]2[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[CH:27][C:26]=1[Cl:32]>>[Cl:32][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:31])[C:25]=1[NH:24][C:18]1[C:17]2[C:22](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:14]([O:33][CH3:34])=[CH:15][CH:16]=2)[O:21][C:20](=[O:23])[CH:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003633558750152588,\"rxn_id\":\"ord-d4de17759f9b43b7a5dcf2c935b7db3d\",\"index\":167694,\"rxn_smiles\":\"C1COCCN1.O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr>>O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"procedure_details\":\"Bromide (204) (0.01 g, 0.22 mmol) prepared as described in example 173 was reacted with morpholine according to the procedure described in example 179 to give amine (210) (73 mg, 72%) as a yellow powder, mp 252\\u2013255° C. 1H NMR δ [(CD3)2SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.62 (m, 2H), 7.57 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J=8.9, 2.5 Hz, 1H), 4.51 (t, J=6.3 Hz, 2H), 3.38 (t, J=4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (t, J=6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 71.19; H, 5.53; N, 9.22.\",\"reactant_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963664412498474,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCN1CCOCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[OH:29][C:9]1[CH:8]=[CH:7][C:6]2[N:5]([CH2:4][CH2:3][CH2:2][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]4[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=4[C:12]=3[C:11]=2[CH:10]=1\",\"yield_000\":72.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037439465522766113,\"rxn_id\":\"ord-be6f8f891af645c9ab74ed3729670458\",\"index\":673332,\"rxn_smiles\":\"C1COCCN1.COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr>>COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"procedure_details\":\"The title compound was prepared from morpholine and 8-(5-bromopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (Example 28) following the procedure outlined in Example 52. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.80 (s, 2H), 7.94 (d, 1H), 7.19 (d, 1H), 4.62 (s, 1H), 3.98 (t, 2H), 3.91 (s, 3H), 3.55 (br, 4H), 2.51-2.15 (br, 6H), 1.69 (m, 2H), 1.47 (m, 4H); MS (ESI): 507.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962560534477234,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCCN1CCOCC1\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:15]([O:34][CH3:35])=[CH:16][CH:17]=[C:18]2[C:23]=1[O:22][C:21](=[O:24])[CH:20]=[C:19]2[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[CH:28][C:27]=1[Cl:33]>>[Cl:33][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([Cl:32])[C:26]=1[NH:25][C:19]1[C:18]2[C:23](=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:15]([O:34][CH3:35])=[CH:16][CH:17]=2)[O:22][C:21](=[O:24])[CH:20]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004199206829071045,\"rxn_id\":\"ord-4d3b8a10f745466aafe4a2248ae64a91\",\"index\":542907,\"rxn_smiles\":\"C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"procedure_details\":\"A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride and brine. The organic layer was dried (MgSO4) and the volatiles were removed by evaporation. The residue was dried under vacuum to give 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.4 g, 83%).\",\"reactant_000\":\"C1CCNCC1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995800793170929,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1\",\"rxn_str\":\"Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:24])[N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH3:26][O:25][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[N:13]=[CH:12][N:11]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:10]2=[O:24]\",\"yield_000\":83.0}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6.1,"literature":"[{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"O\",\"distance\":0.0024762749671936035,\"rxn_id\":\"ord-9206c31e495e40198c626776f18ebc3a\",\"index\":585159,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COC(=O)[C@@H](C)[C@@H]1CCc2cc(O)ccc21.O.O=C([O-])[O-].[Cs+].[Cs+]>>COC(=O)[C@@H](C)[C@@H]1CCc2cc(OCCCBr)ccc21\",\"procedure_details\":\"Methyl (2S)-2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1 yl]propanoate (Example 14) (500 mg, 2.27 mmol), dibromopropane (4.308 g, 21.34 mmol), Cs2CO3 (834 mg, 2.56 mmol), and water (5 drops) were combined in DMF (20 mL) and stirred for 7 h at rt. The reaction mixture was concentrated under reduced pressure, water was added and the aqueous solution was extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc\\/hexane (v\\/v)=1:25) gave 263 mg (34%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 1.08 (d, 3H), 1.91 (m, 1H), 2.17 (m, 1H), 2.32 (m, 2H), 2.80 (m, 1H), 2.88 (m, 2H), 3.51 (m, 1H), 3.61 (t, 2H), 3.72 (s, 3H), 4.08 (t, 2H), 6.69 (d, 1H), 6.76 (s, 1H), 6.98 (d, 1H).\",\"reactant_000\":\"O=C([O-])[O-]\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"COC(=O)[C@@H](C)[C@@H]1CCc2cc(O)ccc21\",\"rxn_time\":7.0,\"reactant_003\":null,\"similarity\":0.9975237250328064,\"agent_000\":\"[Cs+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COC(=O)[C@@H](C)[C@@H]1CCc2cc(OCCCBr)ccc21\",\"rxn_str\":\"[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([C@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])[CH2:6][CH2:5]2.Br[C:18]([Br:21])([CH3:20])C.[C:22]([O-])([O-])=O.[Cs+].[Cs+]>O.CN(C=O)C>[Br:21][CH2:18][CH2:20][CH2:22][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([C@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])[CH2:6][CH2:5]2\",\"yield_000\":34.0},{\"solvent_000\":\"CCC(C)=O\",\"solvent_001\":null,\"distance\":0.0033658742904663086,\"rxn_id\":\"ord-53aae8a75c18456fa8b709f87e828e9f\",\"index\":589545,\"rxn_smiles\":\"CC(C)(Br)Br.CCC(C)=O.O=C([O-])[O-].Oc1ccc2c(c1)oc1cc(Cl)ccc12.[K+].[K+]>>Clc1ccc2c(c1)oc1cc(OCCCBr)ccc12\",\"procedure_details\":\"A mixture of 98.4 g (0.45 mole) of 7-chlorodibenzofuran-3-ol, 200 ml of methyl ethyl ketone, 93 g (0.67 mole) of potassium carbonate and 283 g (1.4 moles) of dibromopropane was refluxed for 24 hours. The inorganic precipitate was filtered off with suction and the filtrate was concentrated under reduced pressure. The residue was dissolved in 500 ml of methylene chloride and the solution was washed with 100 ml of water, 100 ml of 2 N sodium hydroxide solution and 100 ml of water in succession, dried over sodium sulfate and concentrated under reduced pressure. The solid residue was left to stand with 30 ml of pentane at 0° C. for 30 minutes, filtered off with suction and washed with 30 ml of cold n-pentane. 77 g of pure 1-bromo-3-(7-chlorodibenzofuran-3-oxy)-propane of melting point 83°-85° C. were obtained; yield: 50% of theory.\",\"reactant_000\":\"CC(C)(Br)Br\",\"reactant_002\":\"Oc1ccc2c(c1)oc1cc(Cl)ccc12\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9966341257095337,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Clc1ccc2c(c1)oc1cc(OCCCBr)ccc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:15]=[CH:14][C:5]2[C:6]3[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:7]=3[O:8][C:4]=2[CH:3]=1.[C:16](=O)([O-])[O-].[K+].[K+].Br[C:23]([Br:26])([CH3:25])C>C(C(C)=O)C>[Br:26][CH2:23][CH2:25][CH2:16][O:13][C:10]1[CH:11]=[CH:12][C:6]2[C:5]3[CH:14]=[CH:15][C:2]([Cl:1])=[CH:3][C:4]=3[O:8][C:7]=2[CH:9]=1\",\"yield_000\":50.4},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.003755807876586914,\"rxn_id\":\"ord-ad00632e1f604c52987b8464b6586244\",\"index\":429960,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COc1ccc(-c2cc(=O)c3ccc(O)cc3o2)cc1OC.O=C([O-])[O-].[Br-].[K+].[K+].[K+]>>COc1ccc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc1OC\",\"procedure_details\":\"This compound (61) was prepared from 3\\u2032,4\\u2032-dimethoxy-7-hydroxy-flavone, 27 (3 g, 10 mmol), dibromo propane (4 mL, 39.2 mmol) and potassium carbonate (2.8 g, 20 mmol) in dry dimethyl formamide (150 mL) using the identical procedure as described for 56. Yield 3.4 g (80%); mp 148-149° C.; MS (FAB) 419\\/421 (M++1); IR (KBr) 1630; 1H NMR (200 MHz, CDCl3) δ 8.12 (d, J=9.5 Hz, 1H), 7.53 (dd, J=8.5 Hz, 2.0 Hz, 1H), 7.36 (d, J=1.9 Hz, 1H), 6.99-6.95 (m, 3H), 6.68 (s, 1H), 4.24 (t, J=5.8 Hz, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 3.64 (t, J=6.3 Hz, 2H), 2.39 (q, J=6.1 Hz, 2H).\",\"reactant_000\":\"COc1ccc(-c2cc(=O)c3ccc(O)cc3o2)cc1OC\",\"reactant_002\":\"O=C([O-])[O-]\",\"reactant_001\":\"CC(C)(Br)Br\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9962441921234131,\"agent_000\":\"[Br-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc1OC\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:6]1[O:7][C:8]2[C:13]([C:14](=[O:16])[CH:15]=1)=[CH:12][CH:11]=[C:10]([OH:17])[CH:9]=2.Br[C:24]([Br:27])([CH3:26])C.[C:28](=O)([O-])[O-].[K+].[K+].[K+].[Br-]>CN(C)C=O>[Br:27][CH2:24][CH2:26][CH2:28][O:17][C:10]1[CH:9]=[C:8]2[C:13]([C:14](=[O:16])[CH:15]=[C:6]([C:5]3[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:3]([O:2][CH3:1])[CH:4]=3)[O:7]2)=[CH:12][CH:11]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.0038167834281921387,\"rxn_id\":\"ord-8f37b80150c343f895cd5a9ba6cd0eb8\",\"index\":711891,\"rxn_smiles\":\"CC(C)(Br)Br.CN(C)C=O.COc1cc(-c2cc(=O)c3ccc(O)cc3o2)cc(OC)c1OC.O=C([O-])[O-].[Br-].[K+].[K+].[K+]>>COc1cc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc(OC)c1OC\",\"procedure_details\":\"This compound (59) was prepared from 7-hydroxy-3\\u2032,4\\u2032,5\\u2032-trimethoxy-flavone, 25 (3.3 g, 10 mmol), dibromo propane (3 mL, 30 mmol) and potassium carbonate (2.7 g, 20 mmol) in dry dimethyl formamide (120 mL) using the identical procedure as described for 56. Yield 3.1 g (69%); mp 156-157° C.; MS (FAB) 449\\/451 (M++1); IR (KBr) 1629; 1H NMR (200 MHz, CDCl3) δ 8.13 (d, J=9.4 Hz, 1H), 7.11 (s, 2H), 7.01-6.97 (m, 2H), 6.70 (s, 1H), 4.25 (t, J=5.8 Hz, 2H), 3.96 (s, 6H), 3.93 (s, 3H), 3.64 (t, J=6.3 Hz, 2H), 2.39 (q, J=6.1 Hz, 2H).\",\"reactant_000\":\"COc1cc(-c2cc(=O)c3ccc(O)cc3o2)cc(OC)c1OC\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9961832165718079,\"agent_000\":\"[Br-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(-c2cc(=O)c3ccc(OCCCBr)cc3o2)cc(OC)c1OC\",\"rxn_str\":\"[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[CH:7]=[C:8]([C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[O:9]2)=[CH:4][CH:3]=1.Br[C:26]([Br:29])([CH3:28])C.[C:30](=O)([O-])[O-].[K+].[K+].[K+].[Br-]>CN(C)C=O>[Br:29][CH2:26][CH2:28][CH2:30][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[CH:7]=[C:8]([C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[O:9]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":\"CC(=O)OC(C)C\",\"distance\":0.003999054431915283,\"rxn_id\":\"ord-6b7ff184146e44f58a563b737ef5d8b3\",\"index\":342812,\"rxn_smiles\":\"CC(=O)OC(C)C.CC(C)(Br)Br.CCCc1c(O)ccc2c(CC)noc12.CN(C)C=O.O=C([O-])[O-].[Cs+].[Cs+]>>CCCc1c(OCCCBr)ccc2c(CC)noc12\",\"procedure_details\":\"A solution of 3-ethyl-6-hydroxy-7-propylbenz[4,5]isoxazole (2.00 grams; 9.74 mmol) in dry DMF was treated with dibromopropane (7.17 mL; 38.97 mmol) and cesium carbonate (3.49 grams; 10.71 mmol). The solution was stirred at room temperature for 10 hours, then partioned between isopropyl acetate and pH 4.0 buffer. The organic layer was washed twice with water, dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel chromatography afforded the title compound (1.74 g).\",\"reactant_000\":\"CCCc1c(O)ccc2c(CC)noc12\",\"reactant_002\":\"CC(C)(Br)Br\",\"reactant_001\":\"O=C([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9960009455680847,\"agent_000\":\"[Cs+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CCCc1c(OCCCBr)ccc2c(CC)noc12\",\"rxn_str\":\"[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][C:10]([OH:15])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][N:4]=1)[CH3:2].Br[C:17]([Br:20])([CH3:19])C.[C:21](=O)([O-])[O-].[Cs+].[Cs+].C(OC(C)C)(=O)C>CN(C=O)C>[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][C:10]([O:15][CH2:21][CH2:19][CH2:17][Br:20])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][N:4]=1)[CH3:2]\",\"yield_000\":54.8}]","literatureScore":1,"label":"AT UA T5 ER ALL>>164","id":164},"children":[{"depth":4,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":5,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"CC(C)O\",\"solvent_001\":null,\"distance\":0.0018498897552490234,\"rxn_id\":\"ord-1042ad855505453485b72441af00c3ae\",\"index\":498696,\"rxn_smiles\":\"CC(C)O.Nc1cc(Cl)c(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"procedure_details\":\"3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield.\",\"reactant_000\":\"Nc1cc(Cl)c(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.998150110244751,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1F\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([C:6]([F:10])=[CH:7][C:8]=1[Cl:9])[NH2:5].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:25])=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:6]([F:10])=[CH:7][C:8]=1[Cl:9]\",\"yield_000\":78.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0024415254592895508,\"rxn_id\":\"ord-b9793846338c42c8b8f04a17b5fbbd8d\",\"index\":69798,\"rxn_smiles\":\"Nc1cccc(Br)c1.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"procedure_details\":\"3-Bromoaniline is coupled with 4-chloro-7-fluoro-6-nitroquinazoline, to produce 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, which is reacted thereafter with the sodium salt of 3-(4-morpholinyl)-1-propanol, as described hereinabove, to produce 4-[(3-bromophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline. The morpholino-substituted 6-nitroquinazoline is then reduced to the corresponding 6-aminoquinazoline, which is further reacted with bistributyltin, bromine-76 or bromine-77 and acryloyl chloride, as described hereinabove, to yield the final bromine-76 labeled or bromine-77 labeled product.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975584745407104,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1\",\"yield_000\":null},{\"solvent_000\":\"CC(C)O\",\"solvent_001\":\"CC(C)=O\",\"distance\":0.0029898881912231445,\"rxn_id\":\"ord-9b64e283a6044048b2a081954f550360\",\"index\":302864,\"rxn_smiles\":\"CC(C)=O.CC(C)O.Cl.Nc1ccc(Cl)cc1F.O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl>>Cl.O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"procedure_details\":\"A mixture of 4,7-dichloro-6-nitroquinazoline (24.4 g, 0.1 mol), 4-chloro-2-fluoroaniline and ethereal hydrogen chloride (100 ml of a 1M solution) in 2-propanol (600 ml) was heated at reflux for 1.5 hours. The mixture was allowed to cool and diluted with acetone. The solid product was collected by filtration, washed with acetone and dried to give 7-chloro-4-(4-chloro-2-fluoroanilino)-6nitroquinazoline hydrochloride (35.0 g, 90%) as a yellow powder.\",\"reactant_000\":\"Nc1ccc(Cl)cc1F\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9970101118087769,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[C:19]([F:24])[CH:18]=1.Cl>CC(O)C.CC(C)=O>[ClH:1].[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][C:19]=3[F:24])=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":90.0},{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":\"ClCCCl\",\"distance\":0.003641188144683838,\"rxn_id\":\"ord-2167bf1372b54daeb36f51673a3d96e1\",\"index\":116990,\"rxn_smiles\":\"CC(C)(C)O.ClCCCl.Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1.Nc1ccc(F)c(Cl)c1>>Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"procedure_details\":\"To a solution of 7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine (85 mg, 0.34 mmol) in 1,2-dichloroethane\\/t-BuOH (1:1, 2 ml) was added 3-chloro-4-fluoroaniline (50 mg, 0.34 mmol). The mixture was heated at 90° C. for 1 day. After cooling down to room temperature, the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2\\/MeOH 50:1) to yield the title compound as a white solid (0.1 g, 82%).\",\"reactant_000\":\"Fc1ccc(-c2nc3c(Cl)ncnc3o2)cc1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(F)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9963588118553162,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":90.0,\"product_000\":\"Fc1ccc(-c2nc3c(Nc4ccc(F)c(Cl)c4)ncnc3o2)cc1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[F:26])[NH2:22]>ClCCCl.CC(O)(C)C>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[N:10]=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[O:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][C:25]=1[F:26]\",\"yield_000\":82.0},{\"solvent_000\":\"CCCCO\",\"solvent_001\":null,\"distance\":0.0037249326705932617,\"rxn_id\":\"ord-d214e2477e73448fb6ae4ff12a42f15a\",\"index\":193181,\"rxn_smiles\":\"CCCCO.COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1.Nc1cccc(Cl)c1>>COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"procedure_details\":\"6.6 g (25.4 mmol) of 4-chloro-6-(2-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine and 5.34 ml (50.8 mmol) of 3-chloro-aniline in 100 ml of n-butanol are heated at boiling for 1.5 hours. The reaction mixture is cooled, then filtered and washed with diethyl ether and hexane. Flash chromatography (SiO2 ; applied dry; hexane\\/ethyl acetate [2:1] ethanol\\/acetone [1:1]) yields the title compound; m.p. 221-222° C.; TLC-Rf =0.3 (hexane\\/ethyl acetate [1:1]); FAB-MS: (M+H)+ =351.\",\"reactant_000\":\"COc1ccccc1-c1cc2c(Cl)ncnc2[nH]1\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cl)c1\",\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962750673294067,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1-c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1\",\"rxn_str\":\"Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>C(O)CCC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1\",\"yield_000\":null}]","literatureScore":1,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":6,"reaction":{"scalabilityModelScore":6.7,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.010125577449798584,\"rxn_id\":\"ord-e82ad2e910d1448f86a850a6cac03894\",\"index\":490222,\"rxn_smiles\":\"Brc1cccc2cnccc12.O=[N+]([O-])[O-].[K+].[NH4+].[OH-]>>O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"procedure_details\":\"The diethyl ether solution from Example 57A was treated with potassium nitrate (10.1 g, 100 mmol). After stirring for one hour, The mixture was poured onto ice and neutralized with concentrated ammonium hydroxide (˜300 ml). The crude product was collected by filtration, dried, and recrystalization from methanol to provide the title compound (8.83 g).\",\"reactant_000\":\"Brc1cccc2cnccc12\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9898744225502014,\"agent_000\":\"[K+]\",\"agent_001\":\"[NH4+]\",\"agent_002\":\"[OH-]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(Br)c2ccncc12\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>[OH-].[NH4+]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0109785795211792,\"rxn_id\":\"ord-6931e169caf4482eb93b7f99bae1345c\",\"index\":728942,\"rxn_smiles\":\"Brc1ccc2c(c1)CNCC2.O=[N+]([O-])[O-].[K+].[Na+].[OH-]>>O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"procedure_details\":\"In a 5 liter three neck round bottom flask, 173 g (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 mL of concentrated sulfuric add. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric add was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basified to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of methylene chloride. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil, preadsorbed onto silica gel, was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol\\/methylene chloride. The fractions containing product were combined and concentrated to yield 115 g of a solid.\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Brc1ccc2c(c1)CNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9890214204788208,\"agent_000\":\"[K+]\",\"agent_001\":\"[Na+]\",\"agent_002\":\"[OH-]\",\"temperature\":-5.0,\"product_000\":\"O=[N+]([O-])c1cc2c(cc1Br)CNCC2\",\"rxn_str\":\"[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[N+:12]([O-])([O-:14])=[O:13].[K+].[OH-].[Na+]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]\",\"yield_000\":96.2},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015216231346130371,\"rxn_id\":\"ord-536b3c8d1aec427ca9e4004801257f18\",\"index\":349246,\"rxn_smiles\":\"Fc1ccc(C(F)(F)F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"procedure_details\":\"A stirred solution of 2-bromo-4-fluorobenzotrifluoride (1.0 g, 4.1 mmole) in concentrated sulphuric acid (10 ml) at 0° C. was treated portionwise with KNO3 (0.46 g, 4.6 mmole) and maintained at 0° C. for 0.5 hr before warming to room temp. over 2 hr. The mixture was added to well stirred ice\\/water (100 ml) and then extracted with ethyl acetate. The extract was dried and concentrated under vacuum to afford the title compound as a yellow solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3) δ: 7.75 (1H, d), 8.45 (1H, d).\",\"reactant_000\":\"O=[N+]([O-])[O-]\",\"reactant_002\":null,\"reactant_001\":\"Fc1ccc(C(F)(F)F)c(Br)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847837686538696,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=[N+]([O-])c1cc(C(F)(F)F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:13]([O-:15])=[O:14])=[CH:4][C:3]=1[C:9]([F:12])([F:10])[F:11]\",\"yield_000\":101.6},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015547513961791992,\"rxn_id\":\"ord-98cfb85baf744a51b1298ba2672f4e27\",\"index\":678329,\"rxn_smiles\":\"Fc1ccc(F)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"procedure_details\":\"To a stirred solution of 1-bromo-2,5-difluorobenzene (1.000 g, 5.181 mmol, Aldrich, used as received) in conc. H2SO4 (8.0 mL) at 0° C., KNO3 (0.525 g, 5.19 mmol) was added in one lot. The resulting yellow solution was allowed to warm to 28° C. and stirred at 28° C. overnight. It was then poured into ice (80 g) and extracted with ethyl acetate (75 mL). The ethyl acetate was dried over anhydrous Na2SO4, removed under vacuum, and the resulting white solid was dried further under vacuum to afford 1.102 g (89%) of the title compound as a white powder; m.p. 58-60° C.; 1H NMR (CDCl3): δ 7.591 (dd, 1H, J1 =9.6 Hz, J2 =5.4 Hz), 7.891 (t, 1H, J=6.9 Hz).\",\"reactant_000\":\"Fc1ccc(F)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.984452486038208,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":28.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].[N+:10]([O-])([O-:12])=[O:11].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[F:9]\",\"yield_000\":89.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.015690088272094727,\"rxn_id\":\"ord-60b5f559a5d142f49c252464127342c5\",\"index\":206762,\"rxn_smiles\":\"Fc1ccc(Cl)c(Br)c1.O=S(=O)(O)O.O=[N+]([O-])[O-].[K+]>>O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"procedure_details\":\"Potassium nitrate (2.91 g, 28.8 mmol) was gradually added to a stirred solution of 1-bromo-2-chloro-5-fluorobenzene (5 g, 24 mmol) in concentrated sulphuric acid (50 mL) at −5° C. The reaction was stirred for 10 hours then slowly poured in to crushed ice with stirring. The formed precipitate was collected by filtration and dried under reduced pressure to give the title compound (4.7 g, 77%) as a solid.\",\"reactant_000\":\"Fc1ccc(Cl)c(Br)c1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])[O-]\",\"rxn_time\":10.0,\"reactant_003\":null,\"similarity\":0.9843099117279053,\"agent_000\":\"O=S(=O)(O)O\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc(Cl)c(Br)cc1F\",\"rxn_str\":\"[N+:1]([O-:4])([O-])=[O:2].[K+].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[Cl:14]>S(=O)(=O)(O)O>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([N+:1]([O-:4])=[O:2])=[CH:9][C:8]=1[Cl:14]\",\"yield_000\":77.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>460","id":460},"children":[{"depth":7,"reaction":{"label":"AT T5 ER UA ALL>>831","id":831},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"JHBYQJRHJVEKPK","smiles":"FC1=CC2=C(C=C1)C(Cl)=NC=N2","intrinsicScore":0.069,"id":831,"pathId":42}]},{"depth":7,"reaction":{"label":"CF AT T5 UA ALL>>832","id":832},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NHNBFGGVMKEFGY","smiles":"[O-][N+]([O-])=O","intrinsicScore":0.069,"id":832,"pathId":42}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"UYQMNEZWVKRWMS","smiles":"[O-][N+](=O)C1=CC2=C(Cl)N=CN=C2C=C1F","intrinsicScore":0.58,"id":460,"pathId":42}],"RXN":"[cH:11]1[cH:12][c:7]2[c:8]([cH:9][c:10]1[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6].[N+:2](=[O:1])([O-:3])[O-]>>[cH:12]1[c:7]2[c:8]([cH:9][c:10]([c:11]1[N+:2](=[O:1])[O-:3])[F:13])[n:14][cH:15][n:4][c:5]2[Cl:6];10.2.1;Nitration"},{"depth":6,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":42}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":42}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH2:21])[Cl:16])[F:23].[cH:5]1[c:6]2[c:11]([cH:1][c:2]([c:4]1[N+:12](=[O:13])[O-:14])[F:3])[n:10][cH:9][n:8][c:7]2Cl>>[cH:19]1[cH:18][c:17]([c:15]([cH:22][c:20]1[NH:21][c:7]2[c:6]3[cH:5][c:4]([c:2]([cH:1][c:11]3[n:10][cH:9][n:8]2)[F:3])[N+:12](=[O:13])[O-:14])[Cl:16])[F:23];1.3.7;Chloro"},{"depth":5,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":42}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.7,"id":154,"pathId":42}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":4,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>491","id":491},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KQNBBQSOHFVNDL","smiles":"CC(C)(O)Br","intrinsicScore":0.7,"id":491,"pathId":42}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KWSQWZJKAOIFHS","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCBr","intrinsicScore":0.098,"id":164,"pathId":42}],"RXN":"CC(C)(O)Br.c1cc(c(cc1Nc2c3cc(c(cc3ncn2)O)[N+](=O)[O-])Cl)F>>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCBr)[N+](=O)[O-])Cl)F;0.0;Unrecognized"},{"depth":3,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":42}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":42}],"RXN":"[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15]Br)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2].[CH2:27]1[CH2:32][O:31][CH2:30][CH2:29][NH:28]1>>[cH:4]1[cH:3][c:1]([c:25]([cH:24][c:5]1[NH:6][c:7]2[c:8]3[cH:20][c:16]([c:11]([cH:10][c:9]3[n:21][cH:22][n:23]2)[O:12][CH2:13][CH2:14][CH2:15][N:28]4[CH2:27][CH2:32][O:31][CH2:30][CH2:29]4)[N+:17](=[O:19])[O-:18])[Cl:26])[F:2];1.6.2;Bromo"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":42}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":42}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":42}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.802","depth":0,"reaction":{"label":">>0","id":0,"pathId":1785},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.4,"literature":"[{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0018051862716674805,\"rxn_id\":\"ord-3d938035af154af084bfe48b1717a5ff\",\"index\":180426,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 1 g (2.38 mmol) of 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 3.1 g (35.7 mmol) of morpholine, and 0.07 g of sodium iodide in 20 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and ether-hexane was added. One standing, the crystals were deposited giving 1.1 g of the title compound as a off-white solid: mass spectrum (electrospray, m\\/e) M+H 470.9.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9981948137283325,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3ccc(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24]Cl)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1\",\"yield_000\":98.1},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.0023037195205688477,\"rxn_id\":\"ord-89eb09b59b3149a198c2f15b706b551a\",\"index\":9090,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl.[I-].[Na+]>>COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether refluxed for 7 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was recrystallized from ethyl acetate-carbon tetrachloride giving 0.63 of the title compound as a light tan solid: mass spectrum (electrospray, m\\/e) M+H 487.0; (M+2H)+2 243.9.\",\"reactant_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976962804794312,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Nc3cc(O)c(Cl)cc3F)c(C#N)cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH2:25][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:27]#[N:28])=[C:4]([F:29])[CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003024458885192871,\"rxn_id\":\"ord-ef633660b14c4061a6222317d1f19bf8\",\"index\":45028,\"rxn_smiles\":\"C1COCCN1.COc1cc(C#N)c(N)cc1OCCCCl.[I-].[Na+]>>COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of 2-amino-4-chloropropoxy-5-methoxy-benzonitrile (1.000 g, 4.12 mmol), morpholine (1.0 mL) and catalytic amount of sodium iodide were added into a round bottom flask. The solution was stirred and heated under reflux for 2 h. After reaction, extracted the solution with dichloromethane and water, and then combined the organic phases. After evaporating most of the solvent, equivalent amount of hydrochloric acid ether was added into the solution, and filtered to yield 1.100 g of white solid product with a recovery rate of 91%.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C#N)c(N)cc1OCCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9969755411148071,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(C#N)c(N)cc1OCCCN1CCOCC1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]Cl)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[I-].[Na+]>>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:7]([O:15][CH3:16])=[CH:6][C:3]=1[C:4]#[N:5]\",\"yield_000\":null},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.004822194576263428,\"rxn_id\":\"ord-8290e87c12534f90844d32dca1941be9\",\"index\":96846,\"rxn_smiles\":\"C1COCCN1.CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1.CN(C)C=O.[I-].[K+]>>CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"procedure_details\":\"A mixture of 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide (1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassium iodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) was heated at 100° C. for 6 hours. The solution was acidified and extracted with ether to eliminate unreacted products; then the solution was basified and extracted with ether. The solvent was evaporated to dryness to give the product as an oily semisolid which was purified by flash chromatography with dichloromethane:methanol (97:3) as eluent (1.0 g, 87% yield)\",\"reactant_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCCl)c2)s1\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9951778054237366,\"agent_000\":\"[I-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":100.0,\"product_000\":\"CC(C)c1cnc(NC(=O)Cc2cccc(OCCCN3CCOCC3)c2)s1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([NH:15][C:16]2[S:17][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:19][N:20]=2)=[O:14])[CH:9]=[CH:10][CH:11]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[I-].[K+]>CN(C)C=O>[CH:21]([C:18]1[S:17][C:16]([NH:15][C:13](=[O:14])[CH2:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:7]=2)=[N:20][CH:19]=1)([CH3:23])[CH3:22]\",\"yield_000\":87.0},{\"solvent_000\":\"COCCOC\",\"solvent_001\":null,\"distance\":0.005428671836853027,\"rxn_id\":\"ord-1f0333c4478d4fca831ff21e5b4a37f8\",\"index\":225132,\"rxn_smiles\":\"C1COCCN1.COCCOC.COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl.[I-].[Na+]>>COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"procedure_details\":\"Following procedure 1 of Example 149, a mixture of 0.105 g (0.20 mmol) of 8-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile, 0.3 mL of morpholine and 0.01 g of sodium iodide in 10 mL of 1,2-dimethoxyethane is heated under reflux for 7 hours. The resulting solid is purified by silica gel chromatography, utilizing a 98:2 to 94:6 gradient of methylene chloride\\/methanol to give 0.089 g of 4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 205\\u2013208° C.\",\"reactant_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCCl)c(OC)cc4cc23)c(Cl)cc1Cl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994571328163147,\"agent_000\":\"[I-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc(Nc2c(C#N)cnc3cc4cc(OCCCN5CCOCC5)c(OC)cc4cc23)c(Cl)cc1Cl\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:32]([O:33][CH3:34])=[CH:31][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:8]=2[CH:7]=1)[N:15]=[CH:14][C:13]([C:18]#[N:19])=[C:12]3[NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[Cl:30].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[I-].[Na+]>COCCOC>[Cl:30][C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=1[NH:20][C:12]1[C:11]2[C:16](=[CH:17][C:8]3[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:32]([O:33][CH3:34])=[CH:31][C:9]=3[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]#[N:19]\",\"yield_000\":null}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.003534376621246338,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964656233787537,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004257261753082275,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9957427382469177,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004530131816864014,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.995469868183136,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.004715263843536377,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9952847361564636,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.005116403102874756,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9948835968971252,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>34","id":34},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0025193095207214355,\"rxn_id\":\"ord-124e326bb5454329844a7b6365cbc685\",\"index\":479824,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC(F)F.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"procedure_details\":\"0.6 g 60% NaH was added in portions to a solution of 1.23 g 2,2-difluoroethanol in 20 ml THF and stirred at room temperature for 15 minutes. 2.02 g (3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazoline-4-yl)-amine was added as a solid and the mixture was heated to 65° C. for 1 hour, then cooled to room temperature. Water was added and the THF was removed under vacuum. The mixture was sonicated and the resulting solids collected by filtration and dried under vacuum overnight to give 2.93 g of crude (3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9974806904792786,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F\",\"rxn_str\":\"[H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:6][CH2:5][CH:4]([F:7])[F:3])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]\",\"yield_000\":122.5},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.0026805996894836426,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9973194003105164,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.0031785964965820312,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.996821403503418,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.0035967230796813965,\"rxn_id\":\"ord-3796230834af4dd084466ab799f83b80\",\"index\":466982,\"rxn_smiles\":\"CC(C)(C)[O-].CN(C)C=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCC1CC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"procedure_details\":\"29.36 g of cyclopropylmethanol are dissolved in 310 ml of N,N-dimethylformamide and cooled to about 10° C. in an ice bath. Then 41.58 g of potassium tert. butoxide are added batchwise, while the temperature should remain below 15° C. The reaction mixture is then stirred for another 30 minutes at 10° C., after which time 31.19 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline are added batchwise, while again the temperature should not exceed 15° C. The deep red reaction mixture is stirred for another hour at 15° C. For working up, the mixture is poured onto 2.5 l of water and neutralised with 2N hydrochloric acid. The yellowish precipitate formed is suction filtered, washed with water and dried at 50° C. in a drying cupboard.\",\"reactant_000\":\"OCC1CC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9964032769203186,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":10.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](F)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].Cl>CN(C)C=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.0038028955459594727,\"rxn_id\":\"ord-ac23722e65f8452d951a479b9240be9c\",\"index\":159310,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCOC1CCCCO1.[H-].[Na+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"procedure_details\":\"3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"reactant_002\":null,\"reactant_001\":\"OCCOC1CCCCO1\",\"rxn_time\":0.25,\"reactant_003\":null,\"similarity\":0.9961971044540405,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":35.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCOC1CCCCO1\",\"rxn_str\":\"[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]\",\"yield_000\":null}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1785}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1785}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.52,"id":159,"pathId":1785}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"T5 CF UA TTL ER AT LR ALL>>92","id":92},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LAMUXTNQCICZQX","smiles":"OCCCCl","intrinsicScore":0.43,"id":92,"pathId":1785}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.72,"id":165,"pathId":1785}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)F)[N+:19](=[O:20])[O-:21])[Cl:22])[F:4].[CH2:25]([CH2:23][OH:24])[CH2:26][Cl:27]>C1COCC1.[Na]>[cH:6]1[cH:5][c:3]([c:2]([cH:1][c:7]1[NH:8][c:9]2[c:14]3[cH:15][c:16]([c:17]([cH:18][c:13]3[n:12][cH:11][n:10]2)[O:24][CH2:23][CH2:25][CH2:26][Cl:27])[N+:19](=[O:20])[O-:21])[Cl:22])[F:4];1.7.11;SNAr"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LEMMHASEWJSRIA","smiles":"NC1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.035,"id":34,"pathId":1785}],"RXN":"[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[N+:25](=O)[O-])[Cl:8])[F:5]>>[cH:2]1[cH:3][c:4]([c:6]([cH:7][c:1]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:18]([cH:19][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][Cl:24])[NH2:25])[Cl:8])[F:5];7.1.1;Nitro"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.035,"id":9,"pathId":1785}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.66,"id":5,"pathId":1785}],"RXN":"[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29]Cl)[NH2:30])[Cl:14])[F:11].[CH2:2]1[CH2:1][O:6][CH2:5][CH2:4][NH:3]1>[I-].[Na+]>[cH:13]1[cH:12][c:10]([c:9]([cH:8][c:7]1[NH:15][c:16]2[c:21]3[cH:22][c:23]([c:24]([cH:25][c:20]3[n:19][cH:18][n:17]2)[O:26][CH2:27][CH2:28][CH2:29][N:3]4[CH2:2][CH2:1][O:6][CH2:5][CH2:4]4)[NH2:30])[Cl:14])[F:11];1.6.4;Chloro"},{"depth":3,"reaction":{"label":"ER AT T5 UA CF ALL>>326","id":326},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NOUDDDRYIOHXHS","smiles":"OC(O)CCCl","intrinsicScore":0.66,"id":326,"pathId":1785}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDKYXTBSCMZPPR","smiles":"OC(CCCl)NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":82,"pathId":1785}],"RXN":"[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH2:18])[Cl:1])[F:4].[CH2:33]([CH2:32][Cl:31])[CH:34](O)[OH:35]>>[cH:6]1[cH:5][c:3]([c:2]([cH:8][c:7]1[NH:9][c:10]2[c:15]3[cH:16][c:17]([c:19]([cH:30][c:14]3[n:13][cH:12][n:11]2)[O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[NH:18][CH:34]([CH2:33][CH2:32][Cl:31])[OH:35])[Cl:1])[F:4];1.2.9;Alcohol"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":1785}],"RXN":"c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(CCCl)O)Cl)F>C1(C2=C(C=CC=C2)I(OC(C)=O)(OC(C)=O)(OC(=O)C)O1)=O.ClCCl>c1cc(c(cc1Nc2c3cc(c(cc3ncn2)OCCCN4CCOCC4)NC(=O)CCCl)Cl)F;0.0;Unrecognized"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":1785}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.839","depth":0,"reaction":{"label":">>0","id":0,"pathId":182},"children":[{"depth":1,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":2,"reaction":{"scalabilityModelScore":7.3,"literature":"[{\"solvent_000\":\"O=C(O)C(F)(F)F\",\"solvent_001\":null,\"distance\":0.042360901832580566,\"rxn_id\":\"ord-105c1b9741f548d78652c923698b9661\",\"index\":767089,\"rxn_smiles\":\"CCOC(=O)N1C=Cc2c(oc3c(Cl)cc(Br)cc23)CC1.CC[SiH](CC)CC.O=C(O)C(F)(F)F>>CCOC(=O)N1CCc2oc3c(Cl)cc(Br)cc3c2CC1\",\"procedure_details\":\"To a solution of the product of step C (50 mg, 0.13 mmol) and trifluoroacetic acid (0.75 mL) at 0° C. was added triethylsilane (64 μL, 0.40 mmol). The reaction was allowed to warm to ambient temperature over 14 h then quenched by addition of aqueous sodium bicarbonate solution. The mixture was extracted with dichloromethane (2×20 mL) and the combined organic extracts dried over anhydrous Na2SO4, filtered, and the filtrate concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 9:1 to 1:1 hexanes\\/ethyl acetate) to give ethyl 9-bromo-7-chloro-4,5-dihydro-1H-benzofuro[2,3-d]azepine-3(2H)-carboxylate (48 mg, 96%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.45-7.38 (m, 1H), 7.35 (d, J=1.4 Hz, 1H), 4.20 (q, J=7.1 Hz, 2H), 3.78-3.67 (m, 4H), 3.20-3.10 (m, 2H), 2.88-2.75 (m, 2H), 1.29 (t, J=7.0 Hz, 3H).\",\"reactant_000\":\"CCOC(=O)N1C=Cc2c(oc3c(Cl)cc(Br)cc23)CC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9576390981674194,\"agent_000\":\"CC[SiH](CC)CC\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"CCOC(=O)N1CCc2oc3c(Cl)cc(Br)cc3c2CC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([Cl:21])[C:5]2[O:20][C:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:13]=[CH:14][C:8]=3[C:6]=2[CH:7]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>>[Br:1][C:2]1[CH:3]=[C:4]([Cl:21])[C:5]2[O:20][C:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:14][C:8]=3[C:6]=2[CH:7]=1\",\"yield_000\":99.1},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.04490786790847778,\"rxn_id\":\"ord-24fd7b78aed445ca8d261f326e17388d\",\"index\":160670,\"rxn_smiles\":\"CO.NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1Cl.[Pt]>>NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1Cl\",\"procedure_details\":\"A solution of 50 mg (92 μmol) of the compound of Example 58 in 20 ml of methanol was hydrogenated in a continuous-flow hydrogenation apparatus fitted with a 5% Pt\\/C cartridge (H-Cube, from Thales Nano, Budapest, Model HC-2-SS) at a flow rate of 1 ml\\/min, a temperature of 60° C. and at standard pressure. After the reaction had ended, the solution was freed from the methanol on a rotary evaporator and the residue was purified by preparative HPLC [Method 23]. This gave 22 mg (44% of theory) of the title compound.\",\"reactant_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1Cl\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9550921320915222,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1Cl\",\"rxn_str\":\"[C:1](=[O:36])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12](\\/[CH:15]=[CH:16]\\/[C:17]([F:20])([F:19])[F:18])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]>CO.[Pt]>[C:1](=[O:36])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12]([CH2:15][CH2:16][C:17]([F:20])([F:18])[F:19])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.04712486267089844,\"rxn_id\":\"ord-9a361f33f4bc403e93ecdf340d1ca116\",\"index\":486536,\"rxn_smiles\":\"CO.NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F.[Pt]>>NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"procedure_details\":\"A solution of 30 mg (52 μmol) of the compound of Example 61 in 15 ml of methanol was hydrogenated in a continuous-flow hydrogenation apparatus fitted with a 5% Pt\\/C cartridge (H-Cube, from Thales Nano, Budapest, Model HC-2-SS) at a flow rate of 1 ml\\/min, a temperature of 60° C. and at standard pressure. After the reaction had ended, the solution was freed from the methanol on a rotary evaporator and the residue was purified by preparative HPLC [Method 23]. This gave 15 mg (50% of theory) of the title compound.\",\"reactant_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9528751373291016,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)OC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"rxn_str\":\"[C:1](=[O:39])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]([F:38])([F:37])[F:36])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12](\\/[CH:15]=[CH:16]\\/[C:17]([F:20])([F:19])[F:18])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]>CO.[Pt]>[C:1](=[O:39])([O:3][CH:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]([F:37])([F:36])[F:38])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][N:9]1[C:13](=[O:14])[N:12]([CH2:15][CH2:16][C:17]([F:20])([F:18])[F:19])[C:11]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:10]1)[NH2:2]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.04754018783569336,\"rxn_id\":\"ord-3d537ae618694a4088334381873e4a78\",\"index\":49571,\"rxn_smiles\":\"CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O.CO.[Pt]>>CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O\",\"procedure_details\":\"A solution of 25 mg (39 μmol) of the compound of Example 31 in 10 ml of methanol was hydrogenated in an H-Cube fitted with a platinum cartridge (5% Pt\\/C) (continuous-flow hydrogenation apparatus from Thales Nano, Budapest, Model HC-2-SS) at a flow rate of 1 ml\\/min, at 60° C. and under hydrogen at standard pressure. The resulting solution was freed from methanol on a rotary evaporator, and the residue was dissolved in 2 ml of acetonitrile and purified by preparative HPLC [Method 7]. This gave 8 mg (32% of theory) of the title compound.\",\"reactant_000\":\"CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9524598121643066,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(NC(=O)C(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F)C(N)=O\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12](\\/[CH:13]=[CH:14]\\/[C:15]([F:18])([F:17])[F:16])[C:11](=[O:19])[N:10]([CH2:20][C:21]([NH:23][CH:24]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]([F:43])([F:42])[F:41])[C:25]([NH:27][C:28]([CH3:33])([C:30]([NH2:32])=[O:31])[CH3:29])=[O:26])=[O:22])[N:9]=2)=[CH:4][CH:3]=1>CO.[Pt]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][CH2:14][C:15]([F:16])([F:17])[F:18])[C:11](=[O:19])[N:10]([CH2:20][C:21]([NH:23][CH:24]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]([F:41])([F:42])[F:43])[C:25]([NH:27][C:28]([CH3:29])([C:30]([NH2:32])=[O:31])[CH3:33])=[O:26])=[O:22])[N:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.047630906105041504,\"rxn_id\":\"ord-92af5e068d80441da34ed946421d393c\",\"index\":248059,\"rxn_smiles\":\"CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F.CO.[Pt]>>CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"procedure_details\":\"A solution of 168 mg (0.28 mmol) of the compound from Example 146 in 30 ml of methanol was hydrogenated by means of a continuous-flow hydrogenation apparatus (H-Cube, Thales Nano, Budapest, Model HC-2-SS), equipped with a 5% Pt\\/C catalyst cartridge, at 70° C. with a flow rate of 1 ml\\/min under standard pressure. The methanol was removed on a rotary evaporator and the residue was purified by preparative HPLC [Method 20]. This gave 96 mg (55% of theory) of the title compound.\",\"reactant_000\":\"CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(\\/C=C\\/C(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9523690938949585,\"agent_000\":\"[Pt]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCNC(=O)OCC(NC(=O)Cn1nc(-c2ccc(Cl)cc2)n(CCC(F)(F)F)c1=O)c1ccccc1C(F)(F)F\",\"rxn_str\":\"[CH2:1]([NH:3][C:4](=[O:41])[O:5][CH2:6][CH:7]([NH:18][C:19](=[O:40])[CH2:20][N:21]1[C:25](=[O:26])[N:24](\\/[CH:27]=[CH:28]\\/[C:29]([F:32])([F:31])[F:30])[C:23]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=2)=[N:22]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([F:17])([F:16])[F:15])[CH3:2]>CO.[Pt]>[CH2:1]([NH:3][C:4](=[O:41])[O:5][CH2:6][CH:7]([NH:18][C:19](=[O:40])[CH2:20][N:21]1[C:25](=[O:26])[N:24]([CH2:27][CH2:28][C:29]([F:32])([F:31])[F:30])[C:23]([C:33]2[CH:34]=[CH:35][C:36]([Cl:39])=[CH:37][CH:38]=2)=[N:22]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([F:17])([F:16])[F:15])[CH3:2]\",\"yield_000\":null}]","literatureScore":0.96,"label":"LR ALL>>28","id":28},"children":[{"depth":3,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.001256108283996582,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9987438917160034,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.002322077751159668,\"rxn_id\":\"ord-214ad747a1f341d8bd081a26de23f8fc\",\"index\":229462,\"rxn_smiles\":\"CC(=O)O.CCOC(C)=O.O=[N+]([O-])c1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Fe]>>Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"353 mg of iron dissolved in aqueous 5% acetic acid solution was activated at 100° C. 450 mg of [3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-[7 (3-morpholin-4-yl-propoxy)-6-nitro-quinazolin-4-yl]-amine (see, Journal of Medicinal Chemistry 2000, 43, 1380) dissolved in a mixture of ethylacetate and acetic acid (1:1) was added thereto dropwise, and refluxed. The hot reacted solution was filtered under a reduced pressure through celite pad, and the pad was washed with ethylacetate. The washed solvent was washed with saturated sodium bicarbonate solution several times. The organic layer was dried over magnesium sulfate, and filtered and distilled under a reduced pressure to obtain the title compound (353 mg, 83%).\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9976779222488403,\"agent_000\":\"[Fe]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:31][CH2:32][CH2:33][CH2:34][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)=[C:25]([N+:28]([O-])=O)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1>C(O)(=O)C.C(OC(=O)C)C.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:31][CH2:32][CH2:33][CH2:34][N:35]4[CH2:36][CH2:37][O:38][CH2:39][CH2:40]4)=[C:25]([NH2:28])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1\",\"yield_000\":82.8},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0025284886360168457,\"rxn_id\":\"ord-5cc6890b875547de902e23ea2500d6fa\",\"index\":70006,\"rxn_smiles\":\"CCO.O=C([O-])O.O=[N+]([O-])c1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1.[Na+]>>Nc1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1\",\"procedure_details\":\"Stannous chloride dihydrate (478 mg; 2.13 mmol; 5 eq.) was added to a solution of Example 11 (200 mg; 0.43 mmol; 1 eq.) in EtOH (20 mL) and the resulting mixture was stirred at 70° C. for 3 hours, then at room temperature for 16 hours. The solution was diluted with sat. aq. NaHCO3 and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (c-hexane\\/ethyl acetate, 70\\/30) followed by crystallization from n-pentane afforded the title compound as an off-white solid.\",\"reactant_000\":\"O=[N+]([O-])c1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9974715113639832,\"agent_000\":\"O=C([O-])O\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":70.0,\"product_000\":\"Nc1cc(-c2nc(-c3ccccc3OC(F)(F)F)no2)ccc1N1CCCC(F)(F)C1\",\"rxn_str\":\"[F:1][C:2]1([F:33])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][C:26]([F:29])([F:28])[F:27])[N:15]=3)=[CH:10][C:9]=2[N+:30]([O-])=O)[CH2:3]1>CCO.C([O-])(O)=O.[Na+]>[F:33][C:2]1([F:1])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][C:26]([F:27])([F:28])[F:29])[N:15]=3)=[CH:10][C:9]=2[NH2:30])[CH2:3]1\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":\"O\",\"distance\":0.0025320053100585938,\"rxn_id\":\"ord-8be2ef3972144f088e5f0a9bf0a762e6\",\"index\":63590,\"rxn_smiles\":\"CO.O.O=[N+]([O-])c1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1.[Cl-].[Fe].[NH4+]>>Nc1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1\",\"procedure_details\":\"To a mixture of N-(3-(difluoromethoxy)phenyl)-6-nitro-2-(pyrazin-2-yl) quinazolin-4-amine (1.40 g, 3.4 mmol, 1.0 eq.) in MeOH-H2O (v\\/v, 3:1, 110 mL) was added NH4Cl (1.80 g, 34 mmol, 10.0 eq.) and Fe (1.91 g, 34 mmol, 10.0 eq.). The resulting mixture was stirred at 60° C. for 3 h. After the reaction was completed, the mixture was cooled to room temperature, and the iron was filtered off. The filtrate was concentrated to 15 ml, and a precipitate formed and was collected and dried in vacuo to give 1.13 g of N4-(3-(difluoromethoxy)phenyl)-2-(pyrazin-2-yl)quinazoline-4,6-diamine as a pale yellow solid (87.5%). LCMS m\\/z=381.1 (M+1) (Method B) (retention time=1.60 min), 1H-NMR (400 MHz, DMSO-d6): δ 9.69 (s, 1H), 9.52 (d, J=1.2 Hz, 1H), 8.75 (d, J=2.4 Hz, 1H), 8.69 (d, J=2.4 Hz, 1H), 8.30 (s, 1H), 7.87 (dd, J=8.4, 0.8 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.49-7.42 (m, 2H), 7.33-7.32 (m, 1H), 7.31 (t, J=7.4 Hz, 1H), 5.85 (s, 2H).\",\"reactant_000\":\"O=[N+]([O-])c1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9974679946899414,\"agent_000\":\"[Fe]\",\"agent_001\":\"[Cl-]\",\"agent_002\":\"[NH4+]\",\"temperature\":60.0,\"product_000\":\"Nc1ccc2nc(-c3cnccn3)nc(Nc3cccc(OC(F)F)c3)c2c1\",\"rxn_str\":\"[F:1][CH:2]([F:30])[O:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([N+:21]([O-])=O)[CH:19]=3)[N:14]=[C:13]([C:24]3[CH:29]=[N:28][CH:27]=[CH:26][N:25]=3)[N:12]=2)[CH:7]=[CH:8][CH:9]=1.[NH4+].[Cl-]>CO.O.[Fe]>[F:30][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([NH2:21])[CH:19]=3)[N:14]=[C:13]([C:24]3[CH:29]=[N:28][CH:27]=[CH:26][N:25]=3)[N:12]=2)[CH:7]=[CH:8][CH:9]=1\",\"yield_000\":87.4},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0025365352630615234,\"rxn_id\":\"ord-ace4d398f5d9464ba65fd1e3f06cf8c1\",\"index\":464295,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1.[Cl-].[Fe].[NH4+]>>Nc1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1\",\"procedure_details\":\"N-(3-Bromo-5-nitrophenyl)-4-(trifluoromethyl)pyrimidin-2-amine (4.76 g, 13.11 mmol) was dissolved in ethanol (131 ml) and saturated solution of NH4Cl (1 mL) was added followed by Fe (3.66 g, 65.5 mmol). The reaction mixture was stirred at 80° C. for 30 minutes then cooled to room temperature. The solution was filtered through a short pad of silica gel and eluted with EtOAc. The phase were separated, the organics were dried, filtered, concentrated under reduced pressure to afford 5-bromo-N-[4-(trifluoromethyl)pyrimidin-2-yl]benzene-1,3-diamine as a beige powder.\",\"reactant_000\":\"O=[N+]([O-])c1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.5,\"reactant_003\":null,\"similarity\":0.9974634647369385,\"agent_000\":\"[Fe]\",\"agent_001\":\"[Cl-]\",\"agent_002\":\"[NH4+]\",\"temperature\":80.0,\"product_000\":\"Nc1cc(Br)cc(Nc2nccc(C(F)(F)F)n2)c1\",\"rxn_str\":\"[Br:1][C:2]1[CH:3]=[C:4]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:5]=[C:6]([N+:8]([O-])=O)[CH:7]=1.[NH4+].[Cl-]>C(O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[C:4]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:3]=1\",\"yield_000\":null}]","literatureScore":1,"label":"LR ALL>>225","id":225},"children":[{"depth":4,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.014840126037597656,\"rxn_id\":\"ord-1915878c6b4e420da2b4ab481dbec7ab\",\"index\":133760,\"rxn_smiles\":\"C1=C(c2c[nH]c3ccccc23)CCNC1.O=c1c2ccccc2nnn1CCCCl>>O=c1c2ccccc2nnn1CCCN1CC=C(c2c[nH]c3ccccc23)CC1\",\"procedure_details\":\"Starting from 3-(3-chloropropyl)-1,2,3-benzotriazin-4(3H)one (1.49 g, 6.68 mmol) and 3-(1,2,3,6-tetrahydro-4-pyridinyl)1-H-indole (1.32 g, 6.68 mmol), following the same procedure as in example 1, step 3; 2.03 g of 3-[3-(4-(1H-indol-3-yl)-3,6-dihydro-1(2H)-pyridinyl)propyl]-1,2,3-benzotriazin-4(3H)-one was isolated as an off white solid. Yield 79%; mp 189° C.; MS: 386.2 (M+H)+; 1H NMR (300 MHz, CDCl3): δ 2.20 (m, 2H), 2.57 (m, 2H), 2.66 (t, 2H), 2.72 (t, 2H), 3.21 (m, 2H), 4.61 (t, J=5.34 Hz, 2H), 6.15 (t, 1H), 7.12-7.21 (band, 2H), 7.26 (s, 1H), 7.35 (d, 1H), 7.75 (t, 1H), 7.87 (m, 2H), 8.13 (d, 1H), 8.36 (d, 1H).\",\"reactant_000\":\"C1=C(c2c[nH]c3ccccc23)CCNC1\",\"reactant_002\":null,\"reactant_001\":\"O=c1c2ccccc2nnn1CCCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9851598739624023,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=c1c2ccccc2nnn1CCCN1CC=C(c2c[nH]c3ccccc23)CC1\",\"rxn_str\":\"Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:10](=[O:11])[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[N:7]=[N:6]1.[NH:16]1[CH2:21][CH:20]=[C:19]([C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:24][CH:23]=2)[CH2:18][CH2:17]1>>[NH:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:22]([C:19]2[CH2:20][CH2:21][N:16]([CH2:2][CH2:3][CH2:4][N:5]3[C:10](=[O:11])[C:9]4[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=4[N:7]=[N:6]3)[CH2:17][CH:18]=2)=[CH:23]1\",\"yield_000\":78.8},{\"solvent_000\":\"CN(C)C=O\",\"solvent_001\":null,\"distance\":0.016219139099121094,\"rxn_id\":\"ord-b4e4816a8fa14816b80fb331f101738d\",\"index\":194163,\"rxn_smiles\":\"C1CSCCN1.CCNc1cc2ncnc(NCCCCCCl)c2cc1[N+](=O)[O-].CN(C)C=O>>CCNc1cc2ncnc(NCCCCCN3CCSCC3)c2cc1[N+](=O)[O-]\",\"procedure_details\":\"Thiomorpholine (6 ml, 59.7 mmol) was added to a dimethylformamide solution (30 ml) of 4-(5-chloropentylamino)-7-ethylamino-6-nitroquinazoline (2.50 g, 7.41 mmol) obtained in Reference Example 66 and the mixture was heated under reflux for 3 hours. After the solvent was distilled off, the residue was purified by silica gel column chromatography (chloroform:methanol=30:1) to give the title compound (2.95 g, 98.7%).\",\"reactant_000\":\"CCNc1cc2ncnc(NCCCCCCl)c2cc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":\"C1CSCCN1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9837808609008789,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCNc1cc2ncnc(NCCCCCN3CCSCC3)c2cc1[N+](=O)[O-]\",\"rxn_str\":\"[NH:1]1[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1.Cl[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([NH:27][CH2:28][CH3:29])=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1>CN(C)C=O>[CH2:28]([NH:27][C:20]1[CH:19]=[C:18]2[C:23]([C:14]([NH:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][S:4][CH2:3][CH2:2]3)=[N:15][CH:16]=[N:17]2)=[CH:22][C:21]=1[N+:24]([O-:26])=[O:25])[CH3:29]\",\"yield_000\":98.4},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.017159223556518555,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9828407764434814,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.017840802669525146,\"rxn_id\":\"ord-86300bd7508040e69ca3d692d088435d\",\"index\":75105,\"rxn_smiles\":\"COc1ccccc1C=CCCl.ClC(Cl)Cl.Nc1nc2c(s1)CCNCC2>>COc1ccccc1C=CCN1CCc2nc(N)sc2CC1\",\"procedure_details\":\"Prepared from 2-methoxy-cinnamyl chloride and 2 equivalents of 2-amino-4,5,7,8-tetrahydro-6H-thiazolo[5,4-d]azepine in chloroform. Yield: 13% of theory, Melting point: 80°-84° C.\",\"reactant_000\":\"COc1ccccc1C=CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1nc2c(s1)CCNCC2\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9821591973304749,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccccc1C=CCN1CCc2nc(N)sc2CC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[CH:5]=[CH:6][CH2:7]Cl.[NH2:13][C:14]1[S:15][C:16]2[CH2:17][CH2:18][NH:19][CH2:20][CH2:21][C:22]=2[N:23]=1>C(Cl)(Cl)Cl>[NH2:13][C:14]1[S:15][C:16]2[CH2:17][CH2:18][N:19]([CH2:7][CH:6]=[CH:5][C:4]3[CH:9]=[CH:10][CH:11]=[CH:12][C:3]=3[O:2][CH3:1])[CH2:20][CH2:21][C:22]=2[N:23]=1\",\"yield_000\":13.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.017846286296844482,\"rxn_id\":\"ord-fc8a70ac22d6401bb8838ca04cc169ff\",\"index\":499022,\"rxn_smiles\":\"CC(C)(C)OC(=O)NC1CCNCC1.CC1(C)OB(\\/C=C\\\\CCl)OC1(C)C>>CC(C)(C)OC(=O)NC1CCN(C\\/C=C\\/B2OC(C)(C)C(C)(C)O2)CC1\",\"procedure_details\":\"Following the procedure outlined for Example 488, (Z)-2-(3-chloroprop-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (210 mg, 1.1 mmol) was reacted with tert-butyl piperidin-4-ylcarbamate (640 mg, 3.2 mmol) to afford the desired product (100 mg, 30%) as a brown solid: ESI MS m\\/z 367 [C14H27BN2O2+H]+.\",\"reactant_000\":\"CC1(C)OB(\\/C=C\\\\CCl)OC1(C)C\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OC(=O)NC1CCNCC1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9821537137031555,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OC(=O)NC1CCN(C\\/C=C\\/B2OC(C)(C)C(C)(C)O2)CC1\",\"rxn_str\":\"Cl[CH2:2]\\/[CH:3]=[CH:4]\\\\[B:5]1[O:9][C:8]([CH3:11])([CH3:10])[C:7]([CH3:13])([CH3:12])[O:6]1.[NH:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]1>>[CH3:12][C:7]1([CH3:13])[C:8]([CH3:11])([CH3:10])[O:9][B:5](\\/[CH:4]=[CH:3]\\/[CH2:2][N:14]2[CH2:15][CH2:16][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:18][CH2:19]2)[O:6]1\",\"yield_000\":24.8}]","literatureScore":0.99,"label":"T5 AT ER UA TTL ALL>>732","id":732},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.00803530216217041,\"rxn_id\":\"ord-6672941f5a8a49e68bbf94631b4cd77c\",\"index\":130751,\"rxn_smiles\":\"CC#N.COc1cc(C2(C#N)CCC2)c([N+](=O)[O-])cc1O.ClCCCI.O=C([O-])[O-].[K+].[K+]>>COc1cc(C2(C#N)CCC2)c([N+](=O)[O-])cc1OCCCCl\",\"procedure_details\":\"1-(4-(Hydroxyl)-5-methoxy-2-nitrophenyl)cyclobutanecarbonitrile (0.5 g, 2 mmol) in MeCN (10 mL) was treated with potassium carbonate (0.306 g, 2.2 mmol) and 1-chloro-3-iodopropane (0.425 mL, 4 mmol) and stirred at 80° C. for 3 hours. The reaction mixture was concentrated, extracted with dichloromethane and washed with brine. The organic layer was dried (MgSO4), filtered and concentrated. Purification by flash chromatography (silica gel, 5-24% EtOAc\\/hexane) afforded 0.63 g (96%) of 1-(4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl)cyclobutanecarbonitrile. MS (ESI) m\\/z 325 (M+H)+.\",\"reactant_000\":\"ClCCCI\",\"reactant_002\":null,\"reactant_001\":\"COc1cc(C2(C#N)CCC2)c([N+](=O)[O-])cc1O\",\"rxn_time\":3.0,\"reactant_003\":null,\"similarity\":0.9919646978378296,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":80.0,\"product_000\":\"COc1cc(C2(C#N)CCC2)c([N+](=O)[O-])cc1OCCCCl\",\"rxn_str\":\"[OH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11]2)=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:25][CH2:26][CH2:27][CH2:28]I>CC#N>[Cl:25][CH2:26][CH2:27][CH2:28][O:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2([C:14]#[N:15])[CH2:11][CH2:12][CH2:13]2)=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1\",\"yield_000\":97.0},{\"solvent_000\":\"CCC(C)=O\",\"solvent_001\":null,\"distance\":0.009023666381835938,\"rxn_id\":\"ord-a000aaf6e75e491cabc8b097020a6929\",\"index\":231906,\"rxn_smiles\":\"CCC(C)=O.CCCCCCCNC(=O)N(C)c1cccc(-c2ccc(CCC(=O)OC)cc2O)c1.ClCCCI.O=C([O-])[O-].[K+].[K+]>>CCCCCCCNC(=O)N(C)c1cccc(-c2ccc(CCC(=O)OC)cc2OCCCCl)c1\",\"procedure_details\":\"A solution of 300 mg (0.703 mmol, 1 eq) of methyl 3-[3\\u2032-(3-heptyl-1-methylureido)-2-hydroxybiphenyl-4-yl]propanoate (prepared in Example 15f), 319 mg (2.11 mmol, 3 eq) of 1-chloro-3-iodopropane and 583 mg (4.22 mmol, 6 eq) of potassium carbonate in 10 ml of methyl ethyl ketone is refluxed for 7 hours. The insoluble matter is filtered off, the solvent is evaporated off and the oil obtained is chromatographed on silica gel (35 g FlashSmart column) eluted with 60\\/40 heptane\\/ethyl acetate. 394 mg of methyl 3-[2-(3-chloropropoxy)-3\\u2032-(3-heptyl-1-methylureido)biphenyl-4-yl]propanoate are obtained in the form of a yellowish oil. Quantitative yield.\",\"reactant_000\":\"CCCCCCCNC(=O)N(C)c1cccc(-c2ccc(CCC(=O)OC)cc2O)c1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCI\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9909763336181641,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCCCCCCNC(=O)N(C)c1cccc(-c2ccc(CCC(=O)OC)cc2OCCCCl)c1\",\"rxn_str\":\"[CH2:1]([NH:8][C:9](=[O:31])[N:10]([C:12]1[CH:13]=[C:14]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])=[CH:20][C:19]=2[OH:30])[CH:15]=[CH:16][CH:17]=1)[CH3:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[Cl:32][CH2:33][CH2:34][CH2:35]I.C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C>[Cl:32][CH2:33][CH2:34][CH2:35][O:30][C:19]1[CH:20]=[C:21]([CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[CH:22]=[CH:23][C:18]=1[C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([N:10]([CH3:11])[C:9]([NH:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])=[O:31])[CH:13]=1\",\"yield_000\":111.4},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.009926080703735352,\"rxn_id\":\"ord-d400f2b33dff499f83256f56f2ca60c0\",\"index\":172175,\"rxn_smiles\":\"CC#N.Cc1cc([N+](=O)[O-])ccc1O.ClCCCI.O=C([O-])[O-].[K+].[K+]>>Cc1cc([N+](=O)[O-])ccc1OCCCCl\",\"procedure_details\":\"To a stirred solution of 2-methyl-4-nitrophenol (1.0 g, 6.5 mmol) and potassium carbonate (1.8 g, 13.0 mmol) in acetonitrile was added 1-chloro-3-iodopropane (1.2 g, 5.9 mmol). The mixture was heated at reflux overnight then cooled to r.t. and filtered, the solids being further washed with acetonitrile. The combined filtrates were evaporated to dryness. The crude residue was dissolved in ethyl acetate and washed successively with saturated sodium bicarbonate solution, water and brine solution. The organic phase was dried over sodium sulfate, filtered and concentrated to afford 1-(3-chloro-propoxy)-2-methyl-4-nitro-benzene (700 mg, 52%) as an oil.\",\"reactant_000\":\"ClCCCI\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc([N+](=O)[O-])ccc1O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9900739192962646,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc([N+](=O)[O-])ccc1OCCCCl\",\"rxn_str\":\"[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].C(=O)([O-])[O-].[K+].[K+].[Cl:18][CH2:19][CH2:20][CH2:21]I>C(#N)C>[Cl:18][CH2:19][CH2:20][CH2:21][O:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[CH3:1]\",\"yield_000\":51.7},{\"solvent_000\":\"CCOC(C)=O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.01022881269454956,\"rxn_id\":\"ord-409c224910144366a7616095de26a00e\",\"index\":587641,\"rxn_smiles\":\"CCOC(C)=O.CN(C)C=O.COc1ccc(C(=O)N(CCC(C)C)Cc2nc3ccccc3n2Cc2ccccc2O)c(Cl)c1OC.ClCCCI.O=C([O-])[O-].[K+].[K+]>>COc1ccc(C(=O)N(CCC(C)C)Cc2nc3ccccc3n2Cc2ccccc2OCCCCl)c(Cl)c1OC\",\"procedure_details\":\"A solution of 350 mg (0.67 mmole) of (2-chloro-3,4-dimethoxyphenyl)-N-({l-[(2-hydroxyphenyl)methyl] benzimidazol-2-yl}methyl)-N-(3-methylbutyl) carboxamide and 278 mg (2.01 mmole) of K2CO3 in 2 mL of anhydrous N,N-dimethylformamide is treated with 79.1 μL (0.737 mmole) 1-chloro-3-iodo propane at room temperature for 19 hr. The resulting solution is diluted with 60 mL of ethyl acetate, washed with 3×20 mL water and 1×20 mL of brine, dried over anhydrous Na2SO4 and the solvent is removed in vacuo to afford 400 mg (99%) of (2-chloro-3,4-dimethoxyphenyl)-N-[(1-{[2-(3-chloropropoxy)phenyl]methyl}benzimidazol-2-yl)methyl]-N-(3-methylbutyl) carboxamide.\",\"reactant_000\":\"ClCCCI\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc(C(=O)N(CCC(C)C)Cc2nc3ccccc3n2Cc2ccccc2O)c(Cl)c1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9897711873054504,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1ccc(C(=O)N(CCC(C)C)Cc2nc3ccccc3n2Cc2ccccc2OCCCCl)c(Cl)c1OC\",\"rxn_str\":\"[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH3:11])[CH:5]=[CH:4][C:3]=1[C:12]([N:14]([CH2:20][C:21]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[OH:33])[C:24]2[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=2[N:22]=1)[CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:13].C([O-])([O-])=O.[K+].[K+].[Cl:44][CH2:45][CH2:46][CH2:47]I>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH3:11])[CH:5]=[CH:4][C:3]=1[C:12]([N:14]([CH2:20][C:21]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH2:47][CH2:46][CH2:45][Cl:44])[C:24]2[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=2[N:22]=1)[CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:13]\",\"yield_000\":99.7},{\"solvent_000\":\"CC#N\",\"solvent_001\":null,\"distance\":0.012727141380310059,\"rxn_id\":\"ord-a7e1f9f5241e4c1ba0e41ada628eaba2\",\"index\":742467,\"rxn_smiles\":\"CC#N.ICCCCI.O=C([O-])[O-].O=S1(=O)CCN(c2ccc(O)cc2)CC1.[Cs+].[Cs+]>>O=S1(=O)CCN(c2ccc(OCCCCI)cc2)CC1\",\"procedure_details\":\"A mixture of 4-(1',1'-dioxothiomorpholino)phenol (10 g, 44 mmol), 1,4-diiodobutane (40.9 g, 132 mmol) and cesium carbonate (42.9 g, 132 mmol) was heated at 50° C. in acetonitrile (400 ml). After 4 hours, the reaction mixture was cooled, filtered and the solid salts washed with acetonitrile. The filtrate was poured into dilute HCl\\/ice water (1.2 l) and the resultant cream colored solid was isolated by filtration and washed with water. Chromatography on silica gel, with 97:3; dichloromethane:ether, afforded 1-iodo-4-[4'-(1,1-dioxothiomorpholino)phenoxy] butane, II (13.4 g, 74%). Mp. 119-121° C.\",\"reactant_000\":\"O=S1(=O)CCN(c2ccc(O)cc2)CC1\",\"reactant_002\":null,\"reactant_001\":\"ICCCCI\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9872728586196899,\"agent_000\":\"O=C([O-])[O-]\",\"agent_001\":\"[Cs+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S1(=O)CCN(c2ccc(OCCCCI)cc2)CC1\",\"rxn_str\":\"[O:1]=[S:2]1(=[O:15])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[I:16][CH2:17][CH2:18][CH2:19][CH2:20]I.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[I:16][CH2:17][CH2:18][CH2:19][CH2:20][O:14][C:11]1[CH:10]=[CH:9][C:8]([N:5]2[CH2:4][CH2:3][S:2](=[O:1])(=[O:15])[CH2:7][CH2:6]2)=[CH:13][CH:12]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"UA AT ER TTL ALL>>237","id":237},"children":[{"depth":6,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.004299342632293701,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9957006573677063,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.004652976989746094,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9953470230102539,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00585097074508667,\"rxn_id\":\"ord-51bfffc1cc3f48bfba7729fb1fa37a5a\",\"index\":347091,\"rxn_smiles\":\"BrBr.COC(=O)c1sc(-c2ccccc2)cc1O>>COC(=O)c1sc(-c2ccccc2)c(Br)c1O\",\"procedure_details\":\"Prepared by the method described in Example 4 from methyl 3-hydroxy-5-phenyl-2-thiophenecarboxylate (5.0 g, 21 mmoles) and bromine (3.4 g, 21 mmoles). Recrystallization from methanol gave the product (4.0 g); mp 85°-87° C.\",\"reactant_000\":\"COC(=O)c1sc(-c2ccccc2)cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941490292549133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COC(=O)c1sc(-c2ccccc2)c(Br)c1O\",\"rxn_str\":\"[OH:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14].[Br:17]Br>>[OH:1][C:2]1[C:6]([Br:17])=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14]\",\"yield_000\":60.8},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.006023406982421875,\"rxn_id\":\"ord-cec279efa24d480ba329f30936792dee\",\"index\":224777,\"rxn_smiles\":\"BrBr.CC(=O)O.O=C(O)c1cc2ccccc2cc1O>>O=C(O)c1cc2ccccc2c(Br)c1O\",\"procedure_details\":\"3-Hydroxynaphthalene-2-carboxylic acid (3.0 g, 15.9 mmol) was suspended in acetic acid (40 mL) and with vigorous stirring a solution of bromine (817 μL, 15.9 mmol) in acetic acid (10 mL) was added drop wise during 30 minutes. The suspension was stirred at room temperature for 1 hour, filtered and washed with water. Drying in vacuo afforded 3.74 g (88%) of 4-bromo-3-hydroxynaphthalene-2-carboxylic acid as a solid.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"O=C(O)c1cc2ccccc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9939765930175781,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C(O)c1cc2ccccc2c(Br)c1O\",\"rxn_str\":\"[OH:1][C:2]1[C:3]([C:12]([OH:14])=[O:13])=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[Br:15]Br>C(O)(=O)C>[Br:15][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:12]([OH:14])=[O:13])[C:2]=1[OH:1]\",\"yield_000\":88.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.006250619888305664,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9937493801116943,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null}]","literatureScore":1,"label":"UA T5 AT ER TTL ALL>>527","id":527},"children":[{"depth":7,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":8,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":9,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":182}]},{"depth":9,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":182}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":182}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":8,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":182}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.58,"id":154,"pathId":182}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":7,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.58,"id":522,"pathId":182}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"RRIGCTITGHGCKU","smiles":"OC1=C(Br)C2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.78,"id":527,"pathId":182}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[Br:24]Br>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([c:21]([c:7]3[n:8][cH:9][n:10]2)[Br:24])[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];10.1.1;Bromination"},{"depth":6,"reaction":{"label":"T5 AT ER UA TTL ALL>>73","id":73},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"SFOYQZYQTQDRIY","smiles":"ClCCCI","intrinsicScore":0.78,"id":73,"pathId":182}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HWHIMDIPGIVPNT","smiles":"[O-][N+](=O)C1=CC2=C(N=CN=C2NC2=CC(Cl)=C(F)C=C2)C(Br)=C1OCCCCl","intrinsicScore":0.26,"id":237,"pathId":182}],"RXN":"[cH:22]1[cH:23][c:24]([c:26]([cH:28][c:21]1[NH:20][c:19]2[c:12]3[cH:11][c:7]([c:6]([c:14]([c:13]3[n:16][cH:17][n:18]2)[Br:15])[OH:5])[N+:8](=[O:9])[O-:10])[Cl:27])[F:25].[CH2:3]([CH2:1][Cl:2])[CH2:4]I>C(#N)C.O=C([O-])[O-].[K+]>[cH:22]1[cH:23][c:24]([c:26]([cH:28][c:21]1[NH:20][c:19]2[c:12]3[cH:11][c:7]([c:6]([c:14]([c:13]3[n:16][cH:17][n:18]2)[Br:15])[O:5][CH2:4][CH2:3][CH2:1][Cl:2])[N+:8](=[O:9])[O-:10])[Cl:27])[F:25];1.7.9;Williamson"},{"depth":5,"reaction":{"label":"AT UA ER ALL>>925","id":925},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YEEGQDGJIXWFIQ","smiles":"C1COC=CN1","intrinsicScore":0.55,"id":925,"pathId":182}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"LAGYVWYIGZOTJU","smiles":"[O-][N+](=O)C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOC=C1","intrinsicScore":0.75,"id":732,"pathId":182}],"RXN":"[cH:27]1[cH:28][c:29]([c:31]([cH:32][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([c:14]([c:16]3[n:17][cH:18][n:19]2)[Br:15])[O:20][CH2:21][CH2:22][CH2:23]Cl)[N+:24](=[O:26])[O-:25])[Cl:33])[F:30].[CH2:3]1[CH2:4][O:5][CH:6]=[CH:1][NH:2]1>>[cH:27]1[cH:28][c:29]([c:31]([cH:32][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([c:14]([c:16]3[n:17][cH:18][n:19]2)[Br:15])[O:20][CH2:21][CH2:22][CH2:23][N:2]4[CH2:3][CH2:4][O:5][CH:6]=[CH:1]4)[N+:24](=[O:26])[O-:25])[Cl:33])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HIYCMFOTUDUXKH","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOC=C1","intrinsicScore":0.051,"id":225,"pathId":182}],"RXN":"[cH:25]1[cH:26][c:27]([c:28]([cH:29][c:24]1[NH:23][c:2]2[c:1]3[cH:11][c:9]([c:8]([c:7]([c:6]3[n:5][cH:4][n:3]2)[Br:22])[O:12][CH2:13][CH2:14][CH2:15][N:16]4[CH2:21][CH2:20][O:19][CH:18]=[CH:17]4)[N+:10](=O)[O-])[Cl:30])[F:31]>CCO.Cl.[Fe]>[cH:25]1[cH:26][c:27]([c:28]([cH:29][c:24]1[NH:23][c:2]2[c:1]3[cH:11][c:9]([c:8]([c:7]([c:6]3[n:5][cH:4][n:3]2)[Br:22])[O:12][CH2:13][CH2:14][CH2:15][N:16]4[CH2:21][CH2:20][O:19][CH:18]=[CH:17]4)[NH2:10])[Cl:30])[F:31];7.1.1;Nitro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"KZLJLPIWHZPVJS","smiles":"NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C(Br)=C1OCCCN1CCOCC1","intrinsicScore":0.024,"id":28,"pathId":182}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:21]([c:19]([c:18]3[n:17][cH:16][n:15]2)[Br:20])[O:22][CH2:23][CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][O:29][CH:28]=[CH:27]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:21]([c:19]([c:18]3[n:17][cH:16][n:15]2)[Br:20])[O:22][CH2:23][CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)[NH2:1])[Cl:13])[F:11];7.6.1;Alkene"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.79,"id":5,"pathId":182}],"RXN":"[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([c:19]([c:18]3[n:17][cH:16][n:15]2)Br)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11]>>[cH:8]1[cH:9][c:10]([c:12]([cH:14][c:7]1[NH:6][c:5]2[c:4]3[cH:3][c:2]([c:20]([cH:19][c:18]3[n:17][cH:16][n:15]2)[O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[NH2:1])[Cl:13])[F:11];9.7.139;Debromination"},{"depth":1,"reaction":{"label":"T5 AT ER UA TTL ALL>>6","id":6},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"NIXOWILDQLNWCW","smiles":"OC(=O)C=C","intrinsicScore":0.79,"id":6,"pathId":182}]}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":182}],"RXN":"[CH2:4]=[CH:3][C:1](=[O:2])O.[cH:7]1[cH:8][c:9]([c:11]([cH:12][c:6]1[NH:5][c:14]2[c:19]3[cH:20][c:21]([c:22]([cH:33][c:18]3[n:17][cH:16][n:15]2)[O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[NH2:34])[Cl:13])[F:10]>>[CH2:4]=[CH:3][C:1](=[O:2])[NH:34][c:21]1[cH:20][c:19]2[c:18]([cH:33][c:22]1[O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[n:17][cH:16][n:15][c:14]2[NH:5][c:6]4[cH:7][cH:8][c:9]([c:11]([cH:12]4)[Cl:13])[F:10];2.1.2;Carboxylic"},{"pathScore":"-8.846","depth":0,"reaction":{"label":">>0","id":0,"pathId":720},"children":[{"depth":1,"reaction":{"scalabilityModelScore":8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.003969848155975342,\"rxn_id\":\"ord-7070f7b8e48442d392314a63c3b09c6d\",\"index\":49949,\"rxn_smiles\":\"ClCCl.Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1.O=C(Cl)CCCCl>>O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"procedure_details\":\"A solution of EXAMPLE 89 (150 mg, 0.59 mmol) and 4-chlorobutanoyl chloride (83 mg, 0.59 mmol) in dichloromethane (5 mL) was stirred at room temperature for 16 hours, and was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated to provide the title compound. MS (DCI\\/NH3) m\\/z 360 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 1.66-1.73 (m, 4H), 2.07-2.15 (m, 2H), 2.40-2.46 (m, 2H), 2.48-2.51 (m, 2H), 2.50-2.56 (m, 2H), 3.63 (t, J=6.44 Hz, 2H), 3.96 (s, 2H), 6.93 (d, J=7.67 Hz, 1H), 7.21-7.26 (m, 1H), 7.36 (s, 1H), 7.38-7.46 (m, 1H).\",\"reactant_000\":\"O=C(Cl)CCCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9960301518440247,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCCl)Nc1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9](=[O:16])[NH:8][N:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25]>ClCCl>[Cl:20][CH2:21][CH2:22][CH2:23][C:24]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([CH2:5][C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:9](=[O:16])[NH:8][N:7]=2)[CH:3]=1)=[O:25]\",\"yield_000\":null},{\"solvent_000\":\"CCN(C(C)C)C(C)C\",\"solvent_001\":\"C1CCOC1\",\"distance\":0.004049539566040039,\"rxn_id\":\"ord-028e8471258b4354948ce02202245b03\",\"index\":390340,\"rxn_smiles\":\"C1CCOC1.CCN(C(C)C)C(C)C.Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"procedure_details\":\"2 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)-ethyl]piperazine and 0.82 g of Hunig base are introduced into 40 ml of tetrahydrofuran, and a solution of 0.8 g of 3-chloropropionic acid chloride is added dropwise thereto. The solution is left to stand overnight. The resulting suspension is concentrated by evaporation and taken up in methylene chloride and water. There is obtained from the organic phase 1-[4-(3-chloropropionylamino)benzoyl]-4-[2-(4-chlorophenyl)-ethyl]piperazine having a melting point of 190°-191°.\",\"reactant_000\":\"O=C(Cl)CCCl\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.99595046043396,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:34][CH2:35][CH2:36][C:37](Cl)=[O:38]>O1CCCC1>[Cl:34][CH2:35][CH2:36][C:37]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:23][CH:24]=1)=[O:38]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"CCN(CC)CC\",\"distance\":0.004398822784423828,\"rxn_id\":\"ord-0137b3d7e2de4412b4da6a0089bd24c3\",\"index\":176693,\"rxn_smiles\":\"C1CCOC1.CCN(CC)CC.Nc1ccc2[nH]ncc2c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"procedure_details\":\"Triethylamine (1.6 ml, 30.0 mmol) was added to a solution of 5-aminoindazole (2.0 g, 15.0 mmol) in tetrahydrofuran (50 ml) at room temperature, followed by adding thereto 3-chloropropionyl chloride (1.43 ml, 15.0 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred. Thereafter, the solid was collected by filtration and dried under reduced pressure to obtain 3-chloro-N-(1H-indazol-5-yl)propanamide (1.49 g, 44%).\",\"reactant_000\":\"Nc1ccc2[nH]ncc2c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9956011772155762,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1ccc2[nH]ncc2c1\",\"rxn_str\":\"C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[Cl:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>O1CCCC1>[Cl:18][CH2:19][CH2:20][C:21]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:22]\",\"yield_000\":44.4},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.005200862884521484,\"rxn_id\":\"ord-2d69748287e5488f91865c0c8c411ebf\",\"index\":15140,\"rxn_smiles\":\"ClCCl.Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1.O=C(Cl)CCCl>>O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"procedure_details\":\"To a solution of (E)-3-((5-(3-aminophenyl)furan-2-yl)methylene)indolin-2-one (80 mg, 0.26 mmol) and TEA (0.11 mL, 0.79 mol) in DCM (5.0 mL) was added 3-chloropropanoyl chloride (0.04 mL, 0.42 mmol). The reaction was stirred for 20 min and the precipitate was collected by filtration to yield desired (E)-3-chloro-N-(3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)phenyl)propanamide. LCMS (ES): m\\/z 357 [M+1-Cl]+.\",\"reactant_000\":\"Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9947991371154785,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(CCCl)Nc1cccc(-c2ccc(\\/C=C3\\/C(=O)Nc4ccccc43)o2)c1\",\"rxn_str\":\"[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:24][CH2:25][CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:12][C:11](\\/[CH:13]=[C:14]3\\/[C:15](=[O:23])[NH:16][C:17]4[C:22]\\/3=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:10][CH:9]=2)[CH:3]=1)=[O:28]\",\"yield_000\":null},{\"solvent_000\":\"ClCCCl\",\"solvent_001\":\"ClCCl\",\"distance\":0.0052040815353393555,\"rxn_id\":\"ord-dfa8a7e0902b43f7b8d681a409315afe\",\"index\":437265,\"rxn_smiles\":\"ClCCCl.ClCCl.Nc1cnc2ccccc2c1Cl.O=C(Cl)CCCl>>O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"procedure_details\":\"A solution of 4-chloroquinolin-3-amine (6.00 g, 33.59 mmol) and 3-chloropropionyl chloride (4.8 mL, 50.39 mmol) dissolved in 200 mL of 1,2-dichloroethane was heated to 50° C. in an oil bath. After 20 hrs the temperature of the oil bath was increased to 90° C. After an additional 26 hours the reaction was cooled to room temperature, diluted with dichloromethane, washed with saturated aqueous K2CO3, H2O, and brine, dried over Na2SO4, and concentrated under reduced pressure to give 7.12 g of 3-chloro-N-(4-chloroquinolin-3-yl)propanamide as a tan solid.\",\"reactant_000\":\"Nc1cnc2ccccc2c1Cl\",\"reactant_002\":null,\"reactant_001\":\"O=C(Cl)CCCl\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9947959184646606,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"O=C(CCCl)Nc1cnc2ccccc2c1Cl\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH2:12].[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>ClCCCl.ClCCl>[Cl:13][CH2:14][CH2:15][C:16]([NH:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[Cl:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:17]\",\"yield_000\":78.8}]","literatureScore":1,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":4.4,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002118229866027832,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9978817701339722,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0031311511993408203,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9968688488006592,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0035955309867858887,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9964044690132141,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.0036191940307617188,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9963808059692383,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003710031509399414,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.9962899684906006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":3,"reaction":{"scalabilityModelScore":8.1,"literature":"[{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.003292560577392578,\"rxn_id\":\"ord-4f6220e202e04739981d5621ad9d638c\",\"index\":313378,\"rxn_smiles\":\"C1COCCN1.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 10 mL volume glass vessel equipped with a stirrer and a thermometer were placed 1.0 g (3.7 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 1.61 g (18.5 mmol) of morpholine, and 4 mL of methanol. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 1.10 g (reaction yield: 93%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9967074394226074,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.1},{\"solvent_000\":\"CCC(C)O\",\"solvent_001\":\"CO\",\"distance\":0.003420710563659668,\"rxn_id\":\"ord-84f5e33c73e84a4698b90763171c520f\",\"index\":560413,\"rxn_smiles\":\"C1COCCN1.CCC(C)O.CO.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 500 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 95.0 g (0.354 mol) of 6-methoxy-7-(3-chloropropoxy)-quinazolin-4-one, 154.2 g (1.77 mol) of morpholine, and 380 mL of sec-butyl alcohol. The resulting mixture was heated to 105° C. under stirring for 18 hours. After the reaction was complete, 380 mL of methanol was added to the reaction mixture. The resulting mixture was stirred at 70° C. for 30 minutes, and cooled to room temperature. The mixture was then stirred for 30 minutes at room temperature. The precipitated crystalline product was filtered, placed in 190 mL of methanol and stirred for washing, again filtered, and dried at 60° C. under reduced pressure to give 104 g (isolated yield: 92%, purity: 98.81% in terms of area percentage determined by high performance liquid chromatography) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one as a white crystalline product.\",\"reactant_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":18.0,\"reactant_003\":null,\"similarity\":0.9965792894363403,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(CC)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":92.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.003476381301879883,\"rxn_id\":\"ord-a0c39120b0024a4aacdfde0cb07287d5\",\"index\":518855,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl>>COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599\\/601.\",\"reactant_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCCl\",\"reactant_002\":null,\"reactant_001\":\"C1COCCN1\",\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9965236186981201,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"COc1cc2c(Nc3c(Br)cc(C#CC(C)OC)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0037140250205993652,\"rxn_id\":\"ord-8919a99b6db34316ab0f93c2d60f4b88\",\"index\":748620,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 25 mL volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.0 g (7.4 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, and 6.45 g (74 mmol) of morpholine. The resulting mixture was stirred at 105° C. for 4 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 2.17 g (reaction yield: 92%) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.9962859749794006,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":105.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":91.8},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0038033127784729004,\"rxn_id\":\"ord-dcab6d82c32e4baa9d069a31b1022480\",\"index\":95682,\"rxn_smiles\":\"C1COCCN1.COc1cc2c(=O)[nH]cnc2cc1OCCCCl.[Na+].[OH-]>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"In a 5 mL volume glass vessel equipped with a stirrer and a thermometer were placed 0.5 g (1.9 mmol) of 6-methoxy-7-(3-chloropropoxy)quinazolin-4-one prepared by procedures similar to those of Reference Example V-1, 0.5 g (5.7 mmol) of morpholine, and 1.0 mL (4.0 mmol) of aqueous sodium hydroxide solution (4.0 mol\\/L). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction was complete, the reaction mixture was analyzed by high performance liquid chromatography (absolute quantitative analysis). There was produced 0.57 g (reaction yield: 94%) of 6-methoxy-7-(3-morpholinopropoxy)-quinazolin-4-one.\",\"reactant_000\":\"C1COCCN1\",\"reactant_002\":null,\"reactant_001\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCCl\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9961966872215271,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":50.0,\"product_000\":\"COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16]Cl)[N:9]=[CH:8][NH:7][C:6]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:9]=[CH:8][NH:7][C:6]2=[O:18]\",\"yield_000\":93.9}]","literatureScore":1,"label":"T5 ER AT UA TTL ALL>>23","id":23},"children":[{"depth":4,"reaction":{"scalabilityModelScore":7.5,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.004968404769897461,\"rxn_id\":\"ord-67cd89c92ec043eaa8c192a52c6055e1\",\"index\":71209,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)c(F)c2)cc1>>N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"procedure_details\":\"The product from Example 167A and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (99% yield). 1HNMR (300 MHz, CDCl3) δ2.30 (m, 2H), 3.80 (m, 2H), 4.25 (m, 2H), 7.12-7.75 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)c(F)c2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950315952301025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)c(F)c2)cc1\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)=[CH:3][C:2]=1[F:1]\",\"yield_000\":99.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005435526371002197,\"rxn_id\":\"ord-593d5907c892416383020940bf139801\",\"index\":592545,\"rxn_smiles\":\"ClCCCBr.N#Cc1ccc(-c2ccc(O)cc2)cc1F>>N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"procedure_details\":\"The product from Example 166B and 1-bromo-3-chloropropane were processed as described in Example 164C to provide the title compound (98% yield). 1HNMR (300 MHz, CDCl3) δ2.25 (m, 2H), 3.80 (m, 2H), 4.20 (m, 2H), 7.00-7.65 (m, 7H); MS (DCI) m\\/z 290 (M+H)+.\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"N#Cc1ccc(-c2ccc(O)cc2)cc1F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9945644736289978,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1ccc(-c2ccc(OCCCCl)cc2)cc1F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Br[CH2:18][CH2:19][CH2:20][Cl:21]>>[Cl:21][CH2:20][CH2:19][CH2:18][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([F:1])[CH:3]=2)=[CH:11][CH:12]=1\",\"yield_000\":98.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005583524703979492,\"rxn_id\":\"ord-f2089ee29c9c49d6bda509b96fde9e15\",\"index\":355059,\"rxn_smiles\":\"ClCCCBr.Cn1ncc(-c2ccc(O)cc2)cc1=O>>Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"procedure_details\":\"5-[4-(3-Chloro-propoxy)-phenyl]-2-methyl-2H-pyridazin-3-one was prepared from 5-(4-hydroxy-phenyl)-2-methyl-2H-pyridazin-3-one with 1-bromo-3-chloro-propane using the procedure described in Example 86 Step 3; Mp 90-91° C.; MS m\\/z 279 (M+H).\",\"reactant_000\":\"ClCCCBr\",\"reactant_002\":null,\"reactant_001\":\"Cn1ncc(-c2ccc(O)cc2)cc1=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944164752960205,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1ncc(-c2ccc(OCCCCl)cc2)cc1=O\",\"rxn_str\":\"[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]([CH3:14])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0058318376541137695,\"rxn_id\":\"ord-0943760d2d71451cb76c1188d0d02866\",\"index\":410217,\"rxn_smiles\":\"ClCCCBr.O=C1NCCn2c1cc1cc(O)cnc12>>O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"procedure_details\":\"The title compound was synthesized in analogy to example 2, intermediate, from 7-hydroxy-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one (example 84, intermediate a) and 1-bromo-3-chloropropane, to give the desired product as a light yellow solid (80%).\",\"reactant_000\":\"O=C1NCCn2c1cc1cc(O)cnc12\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941681623458862,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1NCCn2c1cc1cc(OCCCCl)cnc12\",\"rxn_str\":\"[OH:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][Cl:20]>>[Cl:20][CH2:19][CH2:18][CH2:17][O:1][C:2]1[CH:14]=[C:13]2[C:5]([N:6]3[C:11](=[CH:12]2)[C:10](=[O:15])[NH:9][CH2:8][CH2:7]3)=[N:4][CH:3]=1\",\"yield_000\":80.0},{\"solvent_000\":\"CC(C)=O\",\"solvent_001\":null,\"distance\":0.006563842296600342,\"rxn_id\":\"ord-cbbf3a06c7d04efaab9b011975b2bcaf\",\"index\":118810,\"rxn_smiles\":\"CC(C)=O.ClCCCBr.O=C1CSc2cc(O)ccc2N1>>O=C1CSc2cc(OCCCCl)ccc2N1\",\"procedure_details\":\"After a mixture consisting of 7-hydroxy-3,4-dihydro-2H-1,4-benzothiazin-3-one (1.812 g, 10 mmol), 1bromo-3-chloropropane (2.362 g, 15 mmol), potassium carbate (4.146 g, 30 mmol) and acetone (40 mmol) was heated under reflux and stirring for 24 hours, insolube matter was filtered off, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel column (developer: chloroform) to purify the same, and was then recrystallized from acetone. The title compound (1.300 g) was obtained as yellow leaflets (yield: 50.4%).\",\"reactant_000\":\"O=C1CSc2cc(O)ccc2N1\",\"reactant_002\":null,\"reactant_001\":\"ClCCCBr\",\"rxn_time\":24.0,\"reactant_003\":null,\"similarity\":0.9934361577033997,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CSc2cc(OCCCCl)ccc2N1\",\"rxn_str\":\"[OH:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.Br[CH2:14][CH2:15][CH2:16][Cl:17].CC(C)=O>>[Cl:17][CH2:16][CH2:15][CH2:14][O:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1\",\"yield_000\":50.4}]","literatureScore":1,"label":"AT T5 ER UA TTL ALL ALL>>165","id":165},"children":[{"depth":5,"reaction":{"scalabilityModelScore":6,"literature":"[{\"solvent_000\":\"CC(C)(C)O\",\"solvent_001\":null,\"distance\":0.004900097846984863,\"rxn_id\":\"ord-90c13fef15b74e0bbc01c05a818beff2\",\"index\":625068,\"rxn_smiles\":\"CC(C)(C)O.O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"procedure_details\":\"A mixture of 2-fluoro-4-(3-thienylmethoxy)nitrobenzene (4.21 g), aqueous potassium hydroxide solution (50 mL; 50% w\\/v) and t-butanol (20 mL) is heated at reflux for 4 hours. It is then evaporated to dryness and the residue is partitioned between ethyl acetate (100 mL) and hydrochloric acid (100 mL; 1 N). The organic phase is washed with water (3×100 mL), dried over magnesium sulphate, filtered and evaporated, to give 2-nitro-5-(3-thienylmethoxy)phenol, in the form of a yellow solid.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9950999021530151,\"agent_000\":\"[K+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1ccc(OCc2ccsc2)cc1O\",\"rxn_str\":\"F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-:18].[K+]>C(O)(C)(C)C>[N+:15]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:7][C:2]=1[OH:18])([O-:17])=[O:16]\",\"yield_000\":null},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.007024884223937988,\"rxn_id\":\"ord-852bc3e0117642e189bf134ac55ba1c4\",\"index\":676092,\"rxn_smiles\":\"C1CCOC1.C[Si](C)(C)[O-].O=[N+]([O-])c1cc(F)c(Br)cc1F.[Na+]>>O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"procedure_details\":\"A solution of 2 M sodium trimethylsilanolate (15.6, 31.1 mmol) in THF was added dropwise to 4-bromo-2,5-difluoronitrobenzene (2.47 g, 10.4 mmol) under a nitrogen atmosphere. A bright red suspension was formed, and the mixture was refluxed for 27 hours. The mixture was cooled to room temperature and concentrated. Water (6 mL) was added, and the solution was acidified with a 10% HCl solution, extracted with DCM (70 mL×2). The organic layers were combined and concentrated to give 5-bromo-4-fluoro-2-nitrophenol (5.05 g, 2.06%). MS m\\/z: 236(M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.48 (d, J=5.87 Hz, 1H), 7.95 (d, J=8.41 Hz, 1H).\",\"reactant_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1F\",\"reactant_002\":null,\"reactant_001\":\"C[Si](C)(C)[O-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.992975115776062,\"agent_000\":\"[Na+]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1cc(F)c(Br)cc1O\",\"rxn_str\":\"C[Si](C)(C)[O-:3].[Na+].[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10](F)[CH:9]=1>C1COCC1>[Br:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([OH:3])[CH:9]=1\",\"yield_000\":205.8},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":\"O\",\"distance\":0.007823646068572998,\"rxn_id\":\"ord-2460b238fde54cbca2e974e36ffeb2ba\",\"index\":585001,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O.O=C(O)c1ccc(F)cc1F.[Na+].[OH-]>>O=C(O)c1ccc(F)cc1O\",\"procedure_details\":\"A solution of 2,4-difluorobenzoic acid (100 g, 0.63 mol) in 1,3-dimethyl-2-imidazolidinone (1,400 mL, 0.45 M) was treated with sodium hydroxide (88 g, 2.2 mol) and heated to 135° C. After stirring for 4 h, the solution was cooled 0° C., dissolved in water (100 mL), and transferred to a 5 L Erlenmeyer flask and carefully treated with aq HCl (2,800 mL, 2 N). After filtering off the crude product, the precipitate was dissolved in ethyl acetate, dried over sodium sulfate and decolorizing charcol, and filtered. The solution was concentrated under reduced pressure and recrystallized from ethyl acetate and heptane to give 4-fluorosalicylic acid (2 crops, 67 g, 68%) as off-white needles. mp: 188-189° C.; Rf 0.26 (20% methanol in dichloromethane).\",\"reactant_000\":\"O=C(O)c1ccc(F)cc1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":4.0,\"reactant_003\":null,\"similarity\":0.992176353931427,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":135.0,\"product_000\":\"O=C(O)c1ccc(F)cc1O\",\"rxn_str\":\"F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-:12].[Na+].Cl>CN1CCN(C)C1=O.O>[F:11][C:9]1[CH:10]=[C:2]([OH:12])[C:3](=[CH:7][CH:8]=1)[C:4]([OH:6])=[O:5]\",\"yield_000\":68.1},{\"solvent_000\":\"CN1CCN(C)C1=O\",\"solvent_001\":null,\"distance\":0.007846713066101074,\"rxn_id\":\"ord-fd2d28a699cd4332b4e4b14ef47e4f83\",\"index\":466187,\"rxn_smiles\":\"CN1CCN(C)C1=O.Cl.O=C(O)c1ccc(F)c(Cl)c1F.[Na+].[OH-]>>O=C(O)c1ccc(F)c(Cl)c1O\",\"procedure_details\":\"Sodium hydroxide (208 g, 5.21 mol) was added in portions to a stirred solution of 3-chloro-2,4-difluorobenzoic acid (200 g, 1.04 mol) in 1,3-dimethyl imidazolidin-2-one (1 L), and the mixture was heated to 140° C. for 2 hours. The reaction mixture was cooled to room temperature and neutralized with ice-cooled 2N HCl (350 mL) precipitating a white solid that was collected by filtration. The filtered solid was dissolved in methyl t-butyl ether (500 mL), washed with saturated brine solution (150 mL) and dried over Na2SO4. Removal of solvent under vacuum afforded the title compound as off white solid. Yield: 180 g (91%). 1H NMR (300 MHz, MeOH-d4) δ: 6.8 (t, 1H), 7.90 (dd, 1H), 11.3 (s, 1H). MS (ES) MH−: 189 for C7H4ClFO3.\",\"reactant_000\":\"O=C(O)c1ccc(F)c(Cl)c1F\",\"reactant_002\":null,\"reactant_001\":\"[OH-]\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9921532869338989,\"agent_000\":\"Cl\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":140.0,\"product_000\":\"O=C(O)c1ccc(F)c(Cl)c1O\",\"rxn_str\":\"[OH-:1].[Na+].[Cl:3][C:4]1[C:5](F)=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8].Cl>CN1CCN(C)C1=O>[Cl:3][C:4]1[C:5]([OH:1])=[C:6]([CH:10]=[CH:11][C:12]=1[F:13])[C:7]([OH:9])=[O:8]\",\"yield_000\":null},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.008236229419708252,\"rxn_id\":\"ord-169c70f529384da2ae8d398e36c8b332\",\"index\":325921,\"rxn_smiles\":\"CCOCC.CS(C)=O.Cl.O.O=[N+]([O-])c1ccc(F)c(Br)c1F.[K+].[OH-]>>O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"procedure_details\":\"A solution of 3-bromo-2,4-difluoro-1-nitrobenzene (10.5 g, 44 mmol) in dimethyl sulfoxide (85 ml) was stirred at ambient temperature. A solution of potassium hydroxide (14.1 g, 251 mmol) in water (21 ml) was added dropwise over 15 minutes. The black reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was then poured onto water (200 ml) and three ether extractions (100 ml) were performed. The aqueous layer was acidified with concentrated hydrochloric acid and extracted three times with ether (100 ml). The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to give a yellow solid (9.7 g, 93% yield). Recrystallization from isopropyl ether afforded an analytical sample: m.p. 65°-66° C. NMR (CDCl3, 60 MHz): 8.1 (dd, 1H, J=10, 5 Hz), 6.8 (dd, 1H, J=10, 8 Hz)\",\"reactant_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1F\",\"reactant_002\":null,\"reactant_001\":\"CCOCC\",\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9917637705802917,\"agent_000\":\"Cl\",\"agent_001\":\"[K+]\",\"agent_002\":\"[OH-]\",\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1ccc(F)c(Br)c1O\",\"rxn_str\":\"[Br:1][C:2]1[C:3](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[K+].CC[O:17]CC.Cl>CS(C)=O.O>[Br:1][C:2]1[C:3]([OH:17])=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":93.0}]","literatureScore":1,"label":"CF T5 AT ER UA TTL ALL ALL>>154","id":154},"children":[{"depth":6,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":7,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":720}]},{"depth":7,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":720}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.074,"id":159,"pathId":720}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":6,"reaction":{"label":"AT T5 ER UA TTL ALL ALL>>27","id":27},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"XLYOFNOQVPJJNP","smiles":"O","intrinsicScore":0.074,"id":27,"pathId":720}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"ODEICIIOTUWISY","smiles":"OC1=CC2=C(C=C1[N+]([O-])=O)C(NC1=CC(Cl)=C(F)C=C1)=NC=N2","intrinsicScore":0.43,"id":154,"pathId":720}],"RXN":"[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)F)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16].[OH-]>>[cH:15]1[cH:14][c:13]([c:11]([cH:10][c:9]1[NH:8][c:7]2[c:5]3[cH:6][c:1]([c:2]([cH:3][c:4]3[n:19][cH:18][n:17]2)O)[N+:20](=[O:22])[O-:21])[Cl:12])[F:16];9.7.66;Fluoro"},{"depth":5,"reaction":{"label":"TTL ALL T5 UA ER ALL>>90","id":90},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"MFESCIUQSIBMSM","smiles":"ClCCCBr","intrinsicScore":0.43,"id":90,"pathId":720}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"OTNGDLBWXZCNIW","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCCl)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.095,"id":165,"pathId":720}],"RXN":"[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[OH:23])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20].[CH2:26]([CH2:25][Cl:24])[CH2:27]Br>>[cH:19]1[cH:18][c:17]([c:15]([cH:14][c:13]1[NH:12][c:11]2[c:6]3[cH:5][c:4]([c:22]([cH:21][c:7]3[n:8][cH:9][n:10]2)[O:23][CH2:27][CH2:26][CH2:25][Cl:24])[N+:1](=[O:3])[O-:2])[Cl:16])[F:20];1.7.9;Williamson"},{"depth":4,"reaction":{"label":"T5 ALL>>9","id":9},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"YNAVUWVOSKDBBP","smiles":"C1COCCN1","intrinsicScore":0.098,"id":9,"pathId":720}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":6,"inchi":"QVZKEQDJKMFEDU","smiles":"[O-][N+](=O)C1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.73,"id":23,"pathId":720}],"RXN":"[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32]Cl)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30].[CH2:1]1[CH2:6][O:5][CH2:4][CH2:3][NH:2]1>C1COCCO1>[cH:24]1[cH:25][c:26]([c:27]([cH:29][c:23]1[NH:22][c:18]2[c:12]3[cH:13][c:14]([c:9]([cH:10][c:11]3[n:21][cH:20][n:19]2)[O:8][CH2:7][CH2:31][CH2:32][N:2]4[CH2:1][CH2:6][O:5][CH2:4][CH2:3]4)[N+:15](=[O:17])[O-:16])[Cl:28])[F:30];1.6.4;Chloro"}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"HBUGOFLVIGUDIA","smiles":"NC1=CC2=C(C=C1OCCCN1CCOCC1)N=CN=C2NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.75,"id":5,"pathId":720}],"RXN":"[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[N+:30](=O)[O-])[Cl:22])[F:24]>>[cH:18]1[cH:19][c:20]([c:21]([cH:23][c:17]1[NH:16][c:15]2[c:14]3[cH:28][c:29]([c:11]([cH:12][c:13]3[n:27][cH:26][n:25]2)[O:10][CH2:9][CH2:1][CH2:2][N:3]4[CH2:4][CH2:5][O:6][CH2:7][CH2:8]4)[NH2:30])[Cl:22])[F:24];7.1.1;Nitro"},{"depth":2,"reaction":{"label":"ER ALL>>70","id":70},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"INUNLMUAPJVRME","smiles":"ClCCC(Cl)=O","intrinsicScore":0.75,"id":70,"pathId":720}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"LPUZPDXDJHYWAC","smiles":"FC1=CC=C(NC2=NC=NC3=CC(OCCCN4CCOCC4)=C(NC(=O)CCCl)C=C23)C=C1Cl","intrinsicScore":0.024,"id":14,"pathId":720}],"RXN":"[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH2:29])[Cl:35])[F:33].[CH2:3]([CH2:4][Cl:5])[C:2](=[O:1])Cl>>[cH:30]1[cH:31][c:32]([c:34]([cH:6][c:7]1[NH:8][c:9]2[c:10]3[cH:11][c:12]([c:13]([cH:14][c:15]3[n:16][cH:17][n:18]2)[O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[NH:29][C:2](=[O:1])[CH2:3][CH2:4][Cl:5])[Cl:35])[F:33];2.1.1;Amide"}],"molecules":[{"commercial":false,"inchi":"OMZCMEYTWSXEPZ","smiles":"C=CC(NC1=C(OCCCN2CCOCC2)C=C(N=CN=C3NC4=CC(Cl)=C(F)C=C4)C3=C1)=O","id":0,"pathId":720}],"RXN":"[cH:4]1[cH:3][c:1]([c:7]([cH:6][c:5]1[NH:9][c:10]2[c:29]3[cH:28][c:27]([c:16]([cH:15][c:14]3[n:13][cH:12][n:11]2)[O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[NH:30][C:31](=[O:32])[CH2:33][CH2:34]Cl)[Cl:8])[F:2]>>[CH2:34]=[CH:33][C:31](=[O:32])[NH:30][c:27]1[cH:28][c:29]2[c:14]([cH:15][c:16]1[O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[n:13][cH:12][n:11][c:10]2[NH:9][c:5]4[cH:4][cH:3][c:1]([c:7]([cH:6]4)[Cl:8])[F:2];9.7.254;Chloro"},{"pathScore":"-8.863","depth":0,"reaction":{"label":">>0","id":0,"pathId":1722},"children":[{"depth":1,"reaction":{"scalabilityModelScore":4.8,"literature":"[{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.026586472988128662,\"rxn_id\":\"ord-e74f3eaa30cb4dfd81fa52a5aa411b54\",\"index\":526742,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC(c2ccc(Br)cc2)OC1>>O=C1CCC(c2ccc(Br)cc2)OC1\",\"procedure_details\":\"To a round bottom flask containing 6-(4-bromophenyl)tetrahydro-2H-pyran-3-ol (638 mg, 2.48 mmol) was added DCM (16 ml). The mixture was stirred at room temperature before Dess-Martin Periodonane (1.3 g, 2.98 mmol) was added in several portions. After the addition, the reaction mixture was stirred for 2 hours before being quenched by a solution of saturated NaHCO3. The organic layer was washed with saturated NaHCO3 twice, then brine. The organic portion was dried over sodium sulfate, filtered and concentrated to afford a crude oil. Column purification afforded the title compound as a thick oil after drying (126 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.55 (m, 2H) 7.26-7.32 (m, 2H) 4.75 (dd, J=10.61, 2.78 Hz, 1H) 4.27-4.36 (m, 1H) 4.14-4.22 (m, 1H) 2.59-2.77 (m, 2H) 2.35 (ddt, J=13.74, 6.60, 3.35, 3.35 Hz, 1H) 2.11-2.24 (m, 1H).\",\"reactant_000\":\"OC1CCC(c2ccc(Br)cc2)OC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9734135270118713,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C1CCC(c2ccc(Br)cc2)OC1\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":20.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02707815170288086,\"rxn_id\":\"ord-8661046706d34fc8b73cc49464677eb4\",\"index\":208142,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC1CCC2CC1CCN2Cc1ccccc1>>O=C1CCC2CC1CCN2Cc1ccccc1\",\"procedure_details\":\"Dess-Martin periodinane (1.30 g) is added to a solution of 2-benzyl-2-aza-bicyclo[3.3.1]nonan-6-ol (0.60 g) in dichloromethane (15 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at ambient temperature for 1 h. Then, the solution is diluted with dichloromethane and washed with a mixture of aqueous Na2S2O3 solution and aqueous NaHCO3 solution. The solution is dried (Na2SO4) and the solvent is removed. The residue is purified by chromatography on silica gel (dichloromethane\\/methanol 1:0→2:1).\",\"reactant_000\":\"OC1CCC2CC1CCN2Cc1ccccc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9729218482971191,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=C1CCC2CC1CCN2Cc1ccccc1\",\"rxn_str\":\"CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][CH:34]2[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[CH2:23]([N:30]1[CH2:37][CH2:36][CH:35]2[CH2:38][CH:31]1[CH2:32][CH2:33][C:34]2=[O:39])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.02808380126953125,\"rxn_id\":\"ord-e352caac2abf4c9ca248f79b087882b6\",\"index\":715589,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1>>O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"procedure_details\":\"(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (Example 1(f)) (2.4 g, 7.54 mmol) was dissolved in 50 mL of DCM and treated with Dess Martin periodinane (3.2 g, 7.54 mmol) and stirred overnight. The next day, the reaction was extracted from 2 M NaOH with DCM (vigorous shaking)×3, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was filtered through a silica gel pad using EtOAc and concentrated to give (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (2.4 g, 100%). MS found: (M+H)+=340.\",\"reactant_000\":\"OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":8.0,\"reactant_003\":null,\"similarity\":0.9719161987304688,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1\",\"rxn_str\":\"[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[OH:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1\",\"yield_000\":100.6},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.02862781286239624,\"rxn_id\":\"ord-98da83649c104f92bc4e8c7dc16bece0\",\"index\":566678,\"rxn_smiles\":\"C1CCOC1.CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12>>O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"procedure_details\":\"To a solution of [3-benzyloxy-2-cyclopropylmethoxy-phenyl]-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (131, 0.99 g, 2.28 mmol) in tetrahydrofuran (120 mL), Dess-Martin periodinane (2.4 g, 5.69 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 50 minutes. The reaction was quenched with a saturated solution of sodium thiosulfate, extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was dried over vacuum to provide the compound as a yellow solid (132, 0.92 g, 93%).\",\"reactant_000\":\"OC(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":0.83,\"reactant_003\":null,\"similarity\":0.9713721871376038,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"O=C(c1cccc(OCc2ccccc2)c1OCC1CC1)c1c[nH]c2ncc(Cl)cc12\",\"rxn_str\":\"[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[C:11]([CH:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)[OH:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([O:27][CH2:28][CH:29]2[CH2:30][CH2:31]2)=[C:11]([C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1\",\"yield_000\":93.2},{\"solvent_000\":\"ClCCl\",\"solvent_001\":null,\"distance\":0.028690993785858154,\"rxn_id\":\"ord-03adc7e6b83d4c9f842ae33ddb550f0b\",\"index\":238884,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.ClCCl.O=C([O-])O.OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21.[Na+]>>O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"procedure_details\":\"The reaction mixture was quenched with saturated sodium bisulfite then was cooled to rt and insoluble materials were removed by filtration. The pH of the filtrate was adjusted to 9 by the addition of a saturated NaHCO3 solution and the organic layer was separated. To the aqueous layer was added saturated NH4Cl solution (5 mL) and it was then extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue, 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-8-ol (3.17 g, 8.30 mmol), was dissolved in methylene chloride (1217 mL, 580 mmol) and Dess-Martin periodinane (3.9 g, 9.20 mmol) was added. The reaction mixture was stirred for 16 h at rt. The reaction mixture was neutralized to pH ˜7 by the addition of NaHCO3, the organic layer was separated, and the aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA\\/hexane) to give the title compound as a white solid (1.34 g, 50% yield). LCMS: (AA) ES+ , 354. 1H NMR (400 MHz, DMSO-d6) δ: 8.51-8.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 8.12-8.18 (m, 1H), 7.51-7.54 (dd, J=1.5 Hz, J=4.5 Hz, 2H), 7.34-7.38 (m, 2H), 7.15-7.17 (br s, 2H), 7.13-7.14 (br s, 1H), 4.26-4.31 (m, 1H), 3.10-3.28 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 2H), 1.50-1.72 (m, 2H).\",\"reactant_000\":\"OC1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":16.0,\"reactant_003\":null,\"similarity\":0.9713090062141418,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"O=C1CCCC(c2ccc(Cl)cc2)c2cc(-c3ccncc3)sc21\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH:12]([OH:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[C:12](=[O:24])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1\",\"yield_000\":45.6}]","literatureScore":0.97,"label":"UA ALL>>14","id":14},"children":[{"depth":2,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CCO\",\"distance\":0.03554779291152954,\"rxn_id\":\"ord-1a59526a75a442dd80a11eab3db55710\",\"index\":515791,\"rxn_smiles\":\"CCO.CCOC(O)C(F)(F)F.Cc1ccc(S(=O)(=O)O)cc1.Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1.O>>CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"procedure_details\":\"A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).\",\"reactant_000\":\"Cn1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1\",\"reactant_002\":null,\"reactant_001\":\"CCOC(O)C(F)(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9644522070884705,\"agent_000\":\"Cc1ccc(S(=O)(=O)O)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(Nc1ccc(Oc2ccnc3cc(-c4cn(C)cn4)sc23)c(F)c1)C(F)(F)F\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=3)[S:17][C:10]=12.[CH2:25]([O:27][CH:28](O)[C:29]([F:32])([F:31])[F:30])[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:25]([O:27][CH:28]([NH:24][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:19]=[CH:20][N:21]([CH3:23])[CH:22]=4)[S:17][C:10]=23)=[C:2]([F:1])[CH:3]=1)[C:29]([F:32])([F:31])[F:30])[CH3:26]\",\"yield_000\":68.7},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.03877246379852295,\"rxn_id\":\"ord-a242bdeb9d274cbc9266b6b2482779a4\",\"index\":73625,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OC1CCCCC1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NC2CCCCC2)c1\",\"procedure_details\":\"200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C\\/15 mm Hg.\",\"reactant_000\":\"OC1CCCCC1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.961227536201477,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1cccc(NC2CCCCC2)c1\",\"rxn_str\":\"[CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":60.0},{\"solvent_000\":\"O\",\"solvent_001\":null,\"distance\":0.040634989738464355,\"rxn_id\":\"ord-da4832067bc14924b62d1946ae82c887\",\"index\":399636,\"rxn_smiles\":\"Cc1cccc(N)c1.O.OCCOc1ccccc1.c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1>>Cc1cccc(NCCOc2ccccc2)c1\",\"procedure_details\":\"138 parts of phenylglycol, 214 parts of m-toluidine and 15 parts of triphenyl phosphite are mixed whilst stirring and next heated to 210° C internal temperature. At this temperature, the elimination of water commences. The mixture is then heated to an internal temperature of 223° C in the course of 9 hours. During this time, 18 parts of water have distilled off and the condensation has ended. The excess starting material is then distilled off. 198 parts of N-(2-phenoxyethyl)-m-toluidine, corresponding to a yield of 87% of theory, distil at a boiling point of 186° - 192° C\\/5 mm Hg.\",\"reactant_000\":\"OCCOc1ccccc1\",\"reactant_002\":null,\"reactant_001\":\"Cc1cccc(N)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9593650102615356,\"agent_000\":\"c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1\",\"agent_001\":null,\"agent_002\":null,\"temperature\":210.0,\"product_000\":\"Cc1cccc(NCCOc2ccccc2)c1\",\"rxn_str\":\"[CH:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9]O)=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[O:7]([CH2:8][CH2:9][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1\",\"yield_000\":87.0},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"CO\",\"distance\":0.041351318359375,\"rxn_id\":\"ord-5aaef5fecf6b464596cd2f9037a9a4df\",\"index\":375977,\"rxn_smiles\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC.CO.Cc1cc(N)cn(C)c1=O.ClCCl>>CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"procedure_details\":\"The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-3-methyl-1H-pyrazole-5-carboxylate (Step 52.3) and 5-amino-1,3-dimethylpyridin-2(1H)-one (Step 20.2). tR: 4.74 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 553 [M+H]+ (LC-MS 2); Rf=0.55 (CH2Cl2\\/MeOH 9:1).\",\"reactant_000\":\"Cc1cc(N)cn(C)c1=O\",\"reactant_002\":null,\"reactant_001\":\"CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.958648681640625,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CCOC(=O)c1c(C(Nc2cc(C)c(=O)n(C)c2)c2ccc(Cl)cc2)c(C)nn1-c1cnc(OC)nc1OC\",\"rxn_str\":\"[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:31][C:32]2[CH:33]=[C:34]([CH3:40])[C:35](=[O:39])[N:36]([CH3:38])[CH:37]=2)[C:9]2[C:10]([CH3:29])=[N:11][N:12]([C:19]3[C:20]([O:27][CH3:28])=[N:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":\"ClCCl\",\"solvent_001\":\"ClCCCl\",\"distance\":0.041440486907958984,\"rxn_id\":\"ord-73e88b5ef78046a69d55bdf4fc626e60\",\"index\":46113,\"rxn_smiles\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21.CC(=O)O[BH-](OC(C)=O)OC(C)=O.COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1.ClCCCl.ClCCl.OCCCF.[Na+]>>COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"procedure_details\":\"To a stirred solution of 3-fluoropropan-1-ol (5 mg, 0.05 mmol) in 0.3 mL o DCM at rt was added Dess-Martin reagent (42 mg, 0.1 mmol). The mixture was stirred for 1 h at rt and 0.3 mL of DCE was added. It was filtered through a cotton pad into a stirred mixture of 4-(7-methoxybenzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)aniline (5 mg, 0.017 mmol, prepared following General Experiment Procedures Q and R) and NaBH(AcO)3 (42 mg, 0.2 mmol) in 0.3 mL of DCE. The reaction was vigorously stirred for 5 min and quenched by adding Na2CO3 (2 mL, saturated). The mixture was extracted with EtOAc (3×5 mL) and the combined organic phase was washed with water (2×10 mL) and dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by reversed phase HPLC (TFA buffered water\\/MeCN) to afford the title compound as an orange solid (5 mg, 53%, TFA salt). MS (ESI) m\\/z [M+H]+351.\",\"reactant_000\":\"OCCCF\",\"reactant_002\":null,\"reactant_001\":\"COc1ccc2nc3nc(-c4ccc(N)cc4)ccn3c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.958559513092041,\"agent_000\":\"CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21\",\"agent_001\":\"CC(=O)O[BH-](OC(C)=O)OC(C)=O\",\"agent_002\":\"[Na+]\",\"temperature\":25.0,\"product_000\":\"COc1ccc2nc3nc(-c4ccc(NCCCF)cc4)ccn3c2c1\",\"rxn_str\":\"[F:1][CH2:2][CH2:3][CH2:4]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:28][O:29][C:30]1[CH:49]=[CH:48][C:33]2[N:34]=[C:35]3[N:40]=[C:39]([C:41]4[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=4)[CH:38]=[CH:37][N:36]3[C:32]=2[CH:31]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][CH2:2][CH2:3][CH2:4][NH:45][C:44]1[CH:46]=[CH:47][C:41]([C:39]2[CH:38]=[CH:37][N:36]3[C:32]4[CH:31]=[C:30]([O:29][CH3:28])[CH:49]=[CH:48][C:33]=4[N:34]=[C:35]3[N:40]=2)=[CH:42][CH:43]=1\",\"yield_000\":83.9}]","literatureScore":0.96,"label":"TTL ALL>>82","id":82},"children":[{"depth":3,"reaction":{"scalabilityModelScore":6.2,"literature":"[{\"solvent_000\":\"CCN(CC)CC\",\"solvent_001\":\"CCO\",\"distance\":0.01522761583328247,\"rxn_id\":\"ord-10ba96c956e94c0689d3d24e36f3db86\",\"index\":50900,\"rxn_smiles\":\"CCN(CC)CC.CCO.Cc1ccc2c(CCN)c[nH]c2c1Br>>Cc1ccc2c(CCN)c[nH]c2c1\",\"procedure_details\":\"A sample of 6-methyl-7-bromo-1H-indole-3-ethanamine was contacted with Pd\\/C H2 in the presence of ethanol and triethylamine. The resulting material was evaporated and partitioned between base\\/CHCl3. The organic phase was dried, concentrated, and dried. The resulting material was taken up into methanol and added to ethereal HCl. The resulting material was washed and vacuum dried.\",\"reactant_000\":\"Cc1ccc2c(CCN)c[nH]c2c1Br\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9847723841667175,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cc1ccc2c(CCN)c[nH]c2c1\",\"rxn_str\":\"[CH3:1][C:2]1[C:10](Br)=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(O)C>C(N(CC)CC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][CH2:13][NH2:14])=[CH:7][NH:8]2)=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0175323486328125,\"rxn_id\":\"ord-7a3f5a36de9042e3b393392d4e02dc98\",\"index\":441223,\"rxn_smiles\":\"Cl.Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F>>Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"procedure_details\":\"m.p. of the hydrochloride: 144°-145° C., was prepared from 1-(4'-amino-3'-bromo-5'-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"Nc1c(Br)cc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9824676513671875,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc(C(O)CNC2CCCC2)cc1C(F)(F)F\",\"rxn_str\":\"Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:13]([OH:21])[CH2:14][NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]([F:10])([F:11])[F:12]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.018399357795715332,\"rxn_id\":\"ord-2964e13611dd46f3a835d3a244df58c5\",\"index\":161960,\"rxn_smiles\":\"Br.N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N>>N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"procedure_details\":\"m.p. of the hydrobromide: >193° C. (decomp.), was prepared from 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclobutylamino-ethanol analogous to Example 51.\",\"reactant_000\":\"N#Cc1cc(C(O)CNC2CCC2)cc(Br)c1N\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9816006422042847,\"agent_000\":\"Br\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"N#Cc1cc(C(O)CNC2CCC2)ccc1N\",\"rxn_str\":\"Br.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:4]=1Br>>[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH:11]([OH:18])[CH2:12][NH:13][CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[C:9]#[N:10]\",\"yield_000\":null},{\"solvent_000\":\"CO\",\"solvent_001\":null,\"distance\":0.018855631351470947,\"rxn_id\":\"ord-efe42b51a2de44018d8a67d343360f2a\",\"index\":148417,\"rxn_smiles\":\"CO.COc1ccc2ncc(N)c(Br)c2n1.O=C([O-])O.[Na+].[Pd]>>COc1ccc2ncc(N)cc2n1\",\"procedure_details\":\"Dissolved 4-bromo-6-(methyloxy)-1,5-naphthyridin-3-amine (as prepared in WO2006081179 A1) (372 mg, 1.464 mmol) in methanol. Added sodium bicarbonate (246 mg, 2.93 mmol) followed by 10% palladium on carbon (312 mg, 0.293 mmol). The mixture was flushed with nitrogen and hydrogenated under balloon pressure for 1 h. After 1 h, filtered reaction mixture and concentrated to afford 155 mg (0.885 mmol, 60%) of the title compound as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 4.05 (s, 3H) 6.90 (d, J=9.09 Hz, 1H) 7.38 (br. s., 1H) 8.16 (d, J=8.84 Hz, 1H) 8.54 (br. s., 1H).\",\"reactant_000\":\"COc1ccc2ncc(N)c(Br)c2n1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.981144368648529,\"agent_000\":\"[Pd]\",\"agent_001\":\"O=C([O-])O\",\"agent_002\":\"[Na+]\",\"temperature\":null,\"product_000\":\"COc1ccc2ncc(N)cc2n1\",\"rxn_str\":\"Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([NH2:14])=[CH:2]2\",\"yield_000\":60.5},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.019538700580596924,\"rxn_id\":\"ord-f8cb66d3303c423b8ce410b382419f62\",\"index\":493646,\"rxn_smiles\":\"Cc1ccccc1.Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21.[Na+].[OH-]>>Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"procedure_details\":\"3.9 cc of toluene containing 2.62 g (0.013 mole) of (CH3OCH2CH2O)2NaAlH2 is added to a solution of 4.13 g (0.0089 mole) of the compound of Example 16 in 80 cc of toluene and the obtained mixture is refluxed with stirring under argon atmosphere. After 6 hours, when the reaction, which is followed by thin layer chromatography, is completed, 100 cc of 5% NaOH is added to the mixture and the toluene phase is separated and washed with a saturated NaCl solution. Upon evaporating the solvent, a crude product is obtained which is recrystallized from ethyl acetate:hexane 1:1, yielding 2 g of the compound of the title. M.p. 144°-46° C.\",\"reactant_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2cc(Br)c3ccccc3c21\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":6.0,\"reactant_003\":null,\"similarity\":0.9804612994194031,\"agent_000\":\"[Na+]\",\"agent_001\":\"[OH-]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"Cn1c(CCN2CCN(Cc3ccccc3)CC2)nc2ccc3ccccc3c21\",\"rxn_str\":\"Br[C:2]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:5]2[N:6]([CH3:24])[C:7]([CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)=[N:8][C:4]=2[CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:17]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:7]2[N:6]([CH3:24])[C:5]3[C:25]4[C:30]([CH:2]=[CH:3][C:4]=3[N:8]=2)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:12][CH2:13]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1\",\"yield_000\":58.4}]","literatureScore":0.98,"label":"ER AT T5 UA CF ALL>>5","id":5},"children":[{"depth":4,"reaction":{"scalabilityModelScore":9.2,"literature":"[{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":null,\"distance\":0.002493739128112793,\"rxn_id\":\"ord-a9f57ab7479a42d492edd74dc06b8313\",\"index\":596542,\"rxn_smiles\":\"C1CCOC1.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1.[Ni]>>Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"The (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy )-6-nitroquinazolin-4-yl]-amine (I) obtained was subsequently hydrogenated inter alia over Raney nickel in THF as solvent to give (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)\",\"reactant_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9975062608718872,\"agent_000\":\"[Ni]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>[Ni].C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]\",\"yield_000\":null},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.00285494327545166,\"rxn_id\":\"ord-96507a19c298432f9c7b776a5ee7e608\",\"index\":174047,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O>>Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"procedure_details\":\"6-[2-Cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-3-nitro-pyridin-2-ol (4.525 g, 12.63 mmol) is dissolved in ethanol (63 mL). The solution is degassed with bubbling nitrogen gas. 10% Pd\\/C (920 mg) is added portionwise to the mixture and the mixture is saturated with hydrogen. The mixture is stirred under a hydrogen atmosphere (balloon) at RT over the weekend, at which time LC\\/MS shows complete conversion. The suspension is filtered through a pad of CELITE® to remove the catalyst and the solution is concentrated under reduced pressure to afford the title compound (3.97 g, 89%). LC-ES\\/MS m\\/z 328.9 (M+1).\",\"reactant_000\":\"O=[N+]([O-])c1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971450567245483,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(-c2nc(C3CC3)[nH]c2-c2ccc(F)cc2F)nc1O\",\"rxn_str\":\"[CH:1]1([C:4]2[NH:5][C:6]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:7]([C:9]3[N:14]=[C:13]([OH:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)[N:8]=2)[CH2:3][CH2:2]1>C(O)C>[NH2:16][C:12]1[C:13]([OH:15])=[N:14][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[NH:5][C:6]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:10][CH:11]=1\",\"yield_000\":95.7},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.002886652946472168,\"rxn_id\":\"ord-3bf6519c914a47c182e19678075a3981\",\"index\":96522,\"rxn_smiles\":\"CCO.Cl.O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1>>Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"procedure_details\":\"Stannous chloride (202.8 mg, 1.07 mmol) was added to a solution of compound 7 (100 mg 0.27 mmol) in ethanol (10 ml) followed by the addition of concentrated HCl (0.5 ml). The reaction mixture was refluxed for 1.5 h and then cooled to 0° C. Yellow precipitate was collected by filtration and then suspended in ethyl acetate. Saturated NaHCO3 was added to adjust pH to 9. Organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (5% MeOH in DCM as developing solvent) to give product 8 (70 mg, Yield: 76%): 1H NMR (200 MHz, CDCl3): δ 8.12 (1H, d, J=2.4 Hz), 7.73 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.29 (2H, d, J=8.5 Hz), 6.84 (2H, m), 6.75 (1H, d, J=8.6 Hz), 6.69 (2H, d, J=8.5 Hz), 4.48 (2H, t, J=4.8 Hz), 3.86 (2H, t, J=4.8 Hz), 3.71 (6H, m), 3.60 (2H, m), 3.32 (3H, b), HRMS (EI) m\\/z calcd. for [C19H24N2O4]+ 344.1736.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9971133470535278,\"agent_000\":\"Cl\",\"agent_001\":null,\"agent_002\":null,\"temperature\":0.0,\"product_000\":\"Nc1ccc(\\/C=C\\/c2ccc(OCCOCCOCCO)nc2)cc1\",\"rxn_str\":\"[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[CH:13][N:12]=1.Cl>C(O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](\\/[CH:17]=[CH:18]\\/[C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)=[CH:13][N:12]=1\",\"yield_000\":75.3},{\"solvent_000\":\"CCO\",\"solvent_001\":null,\"distance\":0.003403782844543457,\"rxn_id\":\"ord-534af4f917274a83a6697124570781ba\",\"index\":627694,\"rxn_smiles\":\"CCO.O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1>>Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"procedure_details\":\"A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.\",\"reactant_000\":\"O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":28.5,\"reactant_003\":null,\"similarity\":0.9965962171554565,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc(C=Cc2ccc(O)cc2)cc1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1\",\"yield_000\":null},{\"solvent_000\":\"Cc1ccccc1\",\"solvent_001\":null,\"distance\":0.003649115562438965,\"rxn_id\":\"ord-613c97c3e8114453bc0fe2abbd04eb15\",\"index\":471188,\"rxn_smiles\":\"Cc1ccccc1.O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1>>Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"procedure_details\":\"Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:\",\"reactant_000\":\"O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"reactant_002\":null,\"reactant_001\":null,\"rxn_time\":1.5,\"reactant_003\":null,\"similarity\":0.996350884437561,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1\",\"rxn_str\":\"[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1\",\"yield_000\":96.1}]","literatureScore":1,"label":"LR ALL>>28","id":28},"children":[{"depth":5,"reaction":{"scalabilityModelScore":7.9,"literature":"[{\"solvent_000\":\"O\",\"solvent_001\":\"CN(C)C=O\",\"distance\":0.006411254405975342,\"rxn_id\":\"ord-73de563950e54f3a8a473ab1f9c7e3c2\",\"index\":86652,\"rxn_smiles\":\"CN(C)C=O.O.O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12.OCC1CC1.[H-].[Na+]>>O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"procedure_details\":\"Cyclopropylmethyl alcohol (0.921 ml, 11.4 mmol) was added to a stirring suspension of NaH (455 mg, 11.4 mmol) in DMF (20 ml) under an argon atmosphere. The resulting solution was allowed to stir at RT for 20 min. 6-chloro-7-fluoro-8-nitro-9H-β-carboline (500 mg, 1.9 mmol) was added to the stirring solution and the resulting mixture was allowed to stir at RT. Upon addition of H2O, a brown solid precipitated out which was filtered to give the desired 6-chloro-7-cyclopropylmethyoxy-8-nitro-9H-β-carboline (510 mg, 85%). 1H-NMR (300 MHz, DMSO-d6): δ 0.35 (m, 2H), 0.59 (m, 2H), 1.32 (m, 1H), 4.04 (d, 2H), 8.21 (d, 1H), 8.46 (d, 1H), 8.90 (s, 1H), 9.02 (s, 1H), 12.32 (b, 1H). Retention Time (LC, method: ammonium acetate standard): 2.63 min. MS (M+H+): 318.\",\"reactant_000\":\"O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12\",\"reactant_002\":null,\"reactant_001\":\"OCC1CC1\",\"rxn_time\":0.33,\"reactant_003\":null,\"similarity\":0.9935887455940247,\"agent_000\":\"[H-]\",\"agent_001\":\"[Na+]\",\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"O=[N+]([O-])c1c(OCC2CC2)c(Cl)cc2c1[nH]c1cnccc12\",\"rxn_str\":\"[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1F)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:19](=[C:20]([N+:23]([O-:25])=[O:24])[C:21]=1[O:5][CH2:4][CH:1]1[CH2:3][CH2:2]1)[NH:18][C:17]1[CH:16]=[N:15][CH:14]=[CH:13][C:12]2=1\",\"yield_000\":84.5},{\"solvent_000\":\"C1CCOC1\",\"solvent_001\":\"O\",\"distance\":0.006817042827606201,\"rxn_id\":\"ord-49c53e1df1d04b21b0eb00386e940407\",\"index\":203432,\"rxn_smiles\":\"C1CCOC1.O.O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F.OCCCN1CCOCC1.[Na]>>O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, J Med Chem, 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc\\/hexane (1:1) to MeOH\\/CH2Cl2\\/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1F\",\"rxn_time\":2.0,\"reactant_003\":null,\"similarity\":0.9931829571723938,\"agent_000\":\"[Na]\",\"agent_001\":null,\"agent_002\":null,\"temperature\":20.0,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3cccc(Br)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1\",\"yield_000\":65.0},{\"solvent_000\":\"CS(C)=O\",\"solvent_001\":\"O\",\"distance\":0.007981956005096436,\"rxn_id\":\"ord-bcba3220bfc145be89ee5b4da6d4edd3\",\"index\":666152,\"rxn_smiles\":\"CC(C)(C)[O-].CS(C)=O.Cl.O.O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F.OCCCN1CCOCC1.[K+]>>O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"procedure_details\":\"6-nitro-4-(3-chloro-4-fluorophenylamino)-7-fluoro-quinazoline (1 eq.) and morpholine-propanol (1.5 eq.) were dissolved in DMSO (10 ml), the solution was stirred for 5 mins with a water bath. A solution of potassium tert-butoxide (3.0 eq.) in DMSO (5 ml) was added slowly to the solution mentioned-above in drops, the mixture was stirred at room temperature for further 30 mins. After the reaction finished, the mixture was diluted with 100 ml water and pH was adjusted to neutral with concentrated hydrochloric acid, then stirred for 30 mins, large amount of yellow solid was precipitated, then filtering, the filter cake was washed with water twice and dried to give yellow solid of N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-6-nitroquinazolin-4-amine (yield 90%).\",\"reactant_000\":\"OCCCN1CCOCC1\",\"reactant_002\":null,\"reactant_001\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1F\",\"rxn_time\":0.08,\"reactant_003\":null,\"similarity\":0.9920180439949036,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"Cl\",\"agent_002\":\"[K+]\",\"temperature\":null,\"product_000\":\"O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1\",\"rxn_str\":\"[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1F)[N:10]=[CH:9][N:8]=[C:7]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1)([O-:3])=[O:2].[N:24]1([CH2:30][CH2:31][CH2:32][OH:33])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+].Cl>CS(C)=O.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:7]2[C:6]3[C:11](=[CH:12][C:13]([O:33][CH2:32][CH2:31][CH2:30][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:21]=[CH:20][C:19]=1[F:22]\",\"yield_000\":90.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00798940658569336,\"rxn_id\":\"ord-e13729e09b02453d8b2ae8502f41e869\",\"index\":593117,\"rxn_smiles\":\"CC(C)(C)[O-].CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-].OCC(F)F.[K+]>>CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"procedure_details\":\"The subtitle compound is prepared from N-(4-bromophenyl)-2-fluoro-4-methylamino-5-nitro-benzamide, 2,2-difluoroethanol and KOtBu in analogy to example 1e.\",\"reactant_000\":\"CNc1cc(F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"reactant_002\":null,\"reactant_001\":\"OCC(F)F\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9920105934143066,\"agent_000\":\"CC(C)(C)[O-]\",\"agent_001\":\"[K+]\",\"agent_002\":null,\"temperature\":null,\"product_000\":\"CNc1cc(OCC(F)F)c(C(=O)Nc2ccc(Br)cc2)cc1[N+](=O)[O-]\",\"rxn_str\":\"[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2F)=[CH:4][CH:3]=1.[F:23][CH:24]([F:27])[CH2:25][OH:26].CC([O-])(C)C.[K+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([NH:19][CH3:20])=[CH:12][C:11]=2[O:26][CH2:25][CH:24]([F:27])[F:23])=[CH:4][CH:3]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008773088455200195,\"rxn_id\":\"ord-c07b2acbc69f47289d653f004b6d071c\",\"index\":64408,\"rxn_smiles\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12.Cl.OCC(F)F.[H-].[Na+]>>COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"procedure_details\":\"Sodium hydride (1.21 g, 30 mmol, as a 60% suspension in mineral oil) was charged into a round bottom flask equipped with magnetic stirring and a nitrogen blanket, washed twice with 10 mL hexanes, dried of residual hexanes under a nitrogen stream, and suspended in 1,2-dimethoxyethane (20 mL). After cooling in an ice bath to about 10° C., 2-fluoro-6-trifluoromethyl-N-(5, 8-di-methoxy[ 1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide (4.21 g, about 98.5% purity, 10 mmol) was added over about 5 min, rinsing in with 1 mL 1,2-dimethoxyethane. A slight exotherm to about 13° C. occurred. Continued ice bath cooling lowered temperature to about 6° C. over about 10 min. To the off-white suspension was added 2,2-difluoroethanol (0.815 niL, 13 mmol) over about 5 min. A slight exotherm to about 13° C. occurred. The light tan suspension was stirred at about 5-10° C. for about 1 hr, then the ice bath was removed. The temperature peaked at about 28° C. (about 2° C. above room temperature) about 0.5 hr later. The tan suspension was stirred overnight (about 20 hr total reaction time), then worked up by addition of the reaction mixture over about 7 min into 5% hydrochloric acid (80 mL, 112 mmol) at about 5-10° C. with ice bath cooling. The suspension was stirred about 18 min at about 9° C., then filtered, washed twice with 15 mL water each, washed twice with 15 mL methanol each, air-dried for about 2 hr, and finally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide to afford the product as a white powder (4.34 g, about 92.8% purity, 8.3 mmol, about 83% yield).\",\"reactant_000\":\"OCC(F)F\",\"reactant_002\":null,\"reactant_001\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(F)cccc3C(F)(F)F)nc12\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9912269115447998,\"agent_000\":\"Cl\",\"agent_001\":\"[H-]\",\"agent_002\":\"[Na+]\",\"temperature\":10.0,\"product_000\":\"COc1cnc(OC)n2nc(NS(=O)(=O)c3c(OCC(F)F)cccc3C(F)(F)F)nc12\",\"rxn_str\":\"[H-].[Na+].F[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15].[F:31][CH:32]([F:35])[CH2:33][OH:34].Cl>>[F:31][CH:32]([F:35])[CH2:33][O:34][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:11])([F:12])[F:13])[C:5]=1[S:14]([NH:17][C:18]1[N:26]=[C:25]2[N:20]([C:21]([O:29][CH3:30])=[N:22][CH:23]=[C:24]2[O:27][CH3:28])[N:19]=1)(=[O:16])=[O:15]\",\"yield_000\":83.0}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>228","id":228},"children":[{"depth":6,"reaction":{"scalabilityModelScore":7,"literature":"[{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.0052683353424072266,\"rxn_id\":\"ord-06c89bc849334262b125339541205942\",\"index\":623693,\"rxn_smiles\":\"BrBr.CC(=O)O.Cc1cc2ncsc2cc1O>>Cc1cc2ncsc2c(Br)c1O\",\"procedure_details\":\"To a suspension of 5-methylbenzo[d]thiazol-6-ol (5C) (140 mg, 0.84 mmol) in acetic acid (5 ml), was added bromine (40 μL) slowly. The reaction mixture was stirred at room temperature for 1 h. The precipitate was collected, washed with acetic acid, water and dried under high vacuum. LCMS-ESI+: calc'd for C8H6BrNOS: 244.0 (M+H+). Found: 244.1 (M+H+).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Cc1cc2ncsc2cc1O\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.9947316646575928,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Cc1cc2ncsc2c(Br)c1O\",\"rxn_str\":\"[CH3:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[Br:12]Br>C(O)(=O)C>[Br:12][C:4]1[C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=[C:2]([CH3:1])[C:3]=1[OH:11]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.005525708198547363,\"rxn_id\":\"ord-6282bcea4e134a849427110b1ae4b3c0\",\"index\":322792,\"rxn_smiles\":\"BrBr.CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O>>CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"procedure_details\":\"Prepared from acetic acid 2-acetoxy-4-(benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (Example 36) according to the procedure of Example 37. White solid: mp 178-179° C.: MS (EI): [M+], 1 bromine isotope pattern, 504, 506; Anal. Calc. for C26H17BrO4S: C, 61.79, H, 3.39, N, 0.00. Found: C, 61.37, H, 3.32, N, 0.11.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"CC(=O)Oc1ccc(-c2c3ccccc3cc3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9944742918014526,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(=O)Oc1ccc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1OC(C)=O\",\"rxn_str\":\"[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2].[Br:32]Br>>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:11]2[C:20]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[S:23][C:19]=3[C:18]([Br:32])=[C:17]3[C:12]=2[CH:13]=[CH:14][CH:15]=[CH:16]3)[CH:8]=[CH:7][C:6]=1[O:28][C:29](=[O:31])[CH3:30])(=[O:3])[CH3:2]\",\"yield_000\":null},{\"solvent_000\":\"CC(=O)O\",\"solvent_001\":null,\"distance\":0.005835771560668945,\"rxn_id\":\"ord-6569ee74ee084f45aee0cc6bab387a3a\",\"index\":556261,\"rxn_smiles\":\"BrBr.CC(=O)O.Nc1ccc2nc(C(F)(F)F)[nH]c2c1>>Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"procedure_details\":\"To a solution of 3.2 g (16 mmol) of 2-trifluoromethyl-5-aminobenzimidazole in 50 ml of AcOH was added 0.34 ml (6.6 mmol) of Br2 dropwise and resulting reaction mixture was stirred for 1 h at 25° C. The reaction mixture was concentrated in vacuo and purified on silica gel column chromatography (10% MeOH\\/CHCl3) to yield 1.7 g (6.2 mmol, 94%) of the desired product.\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1\",\"rxn_time\":1.0,\"reactant_003\":null,\"similarity\":0.994164228439331,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":25.0,\"product_000\":\"Nc1ccc2nc(C(F)(F)F)[nH]c2c1Br\",\"rxn_str\":\"[F:1][C:2]([F:14])([F:13])[C:3]1[NH:4][C:5]2[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[Br:15]Br>CC(O)=O>[F:14][C:2]([F:1])([F:13])[C:3]1[NH:4][C:5]2[C:11]([Br:15])=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1\",\"yield_000\":93.9},{\"solvent_000\":\"O\",\"solvent_001\":\"CC(=O)O\",\"distance\":0.005841076374053955,\"rxn_id\":\"ord-97727426cb48438d86f20a85cb0f4f8f\",\"index\":419983,\"rxn_smiles\":\"BrBr.CC(=O)O.COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O.O>>COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"procedure_details\":\"(3-Chloro-6-hydroxy-5-methoxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (6.9 g) was slurried in acetic acid. A solution of bromine (3.51 g) in acetic acid (31 ml) was gradually added. The reaction mixture was stirred at room temperature and after 15 minutes water (125 ml) was added. The reaction mixture was stirred at cool for 1.5 hours. The solid was filtered and dried in vacuum. The product was a mixture of two compounds and was used for the next step without any purification.\",\"reactant_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2cc1O\",\"reactant_002\":null,\"reactant_001\":\"BrBr\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.994158923625946,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"COc1cc2c(Cl)c(C(=O)N3CCOCC3)sc2c(Br)c1O\",\"rxn_str\":\"[Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([OH:21])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[C:4]2[S:5][C:6]([C:7]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[O:8])=[C:2]([Cl:1])[C:3]=2[CH:18]=[C:17]([O:19][CH3:20])[C:16]=1[OH:21]\",\"yield_000\":null},{\"solvent_000\":\"ClC(Cl)Cl\",\"solvent_001\":null,\"distance\":0.005856215953826904,\"rxn_id\":\"ord-1d443c1852a24a44bc10d8df0c32bd94\",\"index\":784164,\"rxn_smiles\":\"BrBr.ClC(Cl)Cl.Nc1ccc2ncsc2c1>>Nc1ccc2ncsc2c1Br\",\"procedure_details\":\"To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67 mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27 mmol) in CHCl3 (10 ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5:1) to give 7-bromobenzo[d]thiazol-6-amine (80 mg, 80%).\",\"reactant_000\":\"BrBr\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc2ncsc2c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9941437840461731,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"Nc1ccc2ncsc2c1Br\",\"rxn_str\":\"[S:1]1[C:5]2[CH:6]=[C:7]([NH2:10])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Br:11]Br>C(Cl)(Cl)Cl>[Br:11][C:6]1[C:5]2[S:1][CH:2]=[N:3][C:4]=2[CH:9]=[CH:8][C:7]=1[NH2:10]\",\"yield_000\":129.3}]","literatureScore":0.99,"label":"T5 AT ER UA ALL>>528","id":528},"children":[{"depth":7,"reaction":{"scalabilityModelScore":5.3,"literature":"[{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008044242858886719,\"rxn_id\":\"ord-c2eaaaa338594d0597e97fdb4d3efdf7\",\"index\":294045,\"rxn_smiles\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1.Nc1cccc(N2CCOCC2)c1>>CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"procedure_details\":\"Analogous to Example 1510b, 7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (109 mg, 0.37 mmol) and 3-Morpholin-4-yl-phenylamine (0.0818 g, 0.459 mmol) were reacted to afford [7-(3-tert-Butoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as an orange foam (95 mg, 56%). LCMS: 458 (M+H); 1H-NMR (DMSO-d6): 9.30 (s, 1H), 8.97 (s, 1H), 8.06 (s, 1H), 7.98 (d, 1H, J=7.74 Hz), 7.46 (t, 1H, J=7.74), 7.36 (d, 1H, 7.74 Hz), 7.30 (s, 1H), 7.28 (d, 1H, J=9.68 Hz), 7.15 (d, 1H, J=8.07 Hz), 7.12 (d, 1H, J=4.84 Hz), 6.95 (d, 1H, J=4.84 Hz), 4.48 (s, 2H), 3.65 (t, 4H, J=4.58 Hz), 2.95 (t, 4H, J=4.58 Hz), 1.22 (s, 9H).\",\"reactant_000\":\"Nc1cccc(N2CCOCC2)c1\",\"reactant_002\":null,\"reactant_001\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(O)nn23)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9919557571411133,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CC(C)(C)OCc1cccc(-c2ccc3cnc(Nc4cccc(N5CCOCC5)c4)nn23)c1\",\"rxn_str\":\"[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19](O)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[C:1]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[N:21]3[C:16]([CH:17]=[N:18][C:19]([NH:35][C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[CH:30]=4)=[N:20]3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]\",\"yield_000\":56.1},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.0082167387008667,\"rxn_id\":\"ord-187a2ea8a3824696b4f99ec472bc6321\",\"index\":184823,\"rxn_smiles\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1.Nc1ccc(-c2cccnc2)cc1>>CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"procedure_details\":\"[7-(3-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-pyridin-3-yl-phenyl)-amine was prepared from 7-(3-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 4-pyridin-3-yl-phenylamine in an analogous manner to Example 1052a. Product isolated as a yellow solid (66 mg, 49%). m.p.=216-218° C.; LCMS (m\\/e) 442 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.79 (s, 1H), 8.71 (s, 1H), 8.56 (d, 1H, J=4.3 Hz), 8.42 (d, 1H, J=7.9 Hz), 7.95 (d, 1H, J=7.8 Hz), 7.90 (d, 1H, J=8.0 Hz), 7.78-7.68 (m, 3H), 7.64 (d, 2H, J=8.6 Hz), 7.36 (dd, 1H, J=4.9 and 7.7 Hz), 7.09 (d, 1H, J=4.8 Hz), 6.98 (s, 1H), 6.90 (d, 1H, J=4.8 Hz), 3.08 (s, 3H).\",\"reactant_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(-c2cccnc2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9917832612991333,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"CS(=O)(=O)c1cccc(-c2ccc3cnc(Nc4ccc(-c5cccnc5)cc4)nn23)c1\",\"rxn_str\":\"[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17](O)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH:22]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([C:23]5[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=5)=[CH:32][CH:31]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.008971095085144043,\"rxn_id\":\"ord-5bc7d59bbd414b3d985eb84e8c299d4b\",\"index\":500977,\"rxn_smiles\":\"Nc1ccc(C2CCN(CCO)CC2)cc1.O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1>>O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"procedure_details\":\"The compound was prepared in an analogous fashion to Example 522 using 7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol and 2-[4-(4-amino-phenyl)-piperidin-1-yl]-ethanol to provide 2-[4-(4-{7-[3-(pyrrolidine-1-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}phenyl)-piperidin-1-yl]ethanol as a brown lyophilate (49.2 mg, 25% yield). LCMS (E\\/I+) 547 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.22 (broad s, 1H), 9.04 (s, 1H), 8.53 (s, 1H), 8.42 (d, 1H, J=7.6 Hz), 7.82 (m, 2H), 7.70 (d, 2H, J=8.5 Hz), 7.29 (d, 1H, J=4.7 Hz), 7.22 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=4.7 Hz), 3.77 (t, 2H, J=5 Hz), 3.42 (d, 2H, J=11.9 Hz), 3.37 (m, 1H), 3.18 (m, 6H), 3.09 (m, 2H), 2.75 (m, 1H), 1.95 (m, 3H), 1.65 (m, 4H).\",\"reactant_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(O)nn23)c1)N1CCCC1\",\"reactant_002\":null,\"reactant_001\":\"Nc1ccc(C2CCN(CCO)CC2)cc1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.991028904914856,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"O=S(=O)(c1cccc(-c2ccc3cnc(Nc4ccc(C5CCN(CCO)CC5)cc4)nn23)c1)N1CCCC1\",\"rxn_str\":\"[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21](O)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]([C:15]3[N:23]4[C:18]([CH:19]=[N:20][C:21]([NH:25][C:26]5[CH:31]=[CH:30][C:29]([CH:32]6[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][OH:40])[CH2:34][CH2:33]6)=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1\",\"yield_000\":25.0},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.009240865707397461,\"rxn_id\":\"ord-5a6157637ea04ff388b5b7f302663036\",\"index\":34125,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1cccc(F)c1>>NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"procedure_details\":\"Compound 9 was prepared following general synthetic scheme 7 wherein (3-fluorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [298 (M+1)], 1H NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 9.32 (s, 1H), 8.55-8.50 (m, 2H), 8.05 (s, 1H), 7.99 (t, 1H), 7.41-7.35 (m, 1H), 7.26-7.23 (m, 2H), 7.11-7.09 (m, 1H), 4.93 (d, 2H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1cccc(F)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9907591342926025,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3cccc(F)c3)nnnc12\",\"rxn_str\":\"[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.O[C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[C:12]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([NH2:23])=[O:22])[C:13]=2[N:14]=[N:15][N:16]=1\",\"yield_000\":null},{\"solvent_000\":null,\"solvent_001\":null,\"distance\":0.00942915678024292,\"rxn_id\":\"ord-03bfa14da0a648559a9d736cfbfbcce9\",\"index\":199175,\"rxn_smiles\":\"NC(=O)c1cccc2c(O)nnnc12.NCc1ccc(Cl)c(Cl)c1>>NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"procedure_details\":\"Compound 2 was prepared following general synthetic scheme 7 wherein (3,4-dichlorophenyl)methanamine was reacted with 4-hydroxybenzo[d][1,2,3]-triazine-8-carboxamide to give the title compound. LC-MS [350 (M+1)], 1H NMR (400 MHz, DMSO-d6): δ 9.37 (s, 1H), 9.31 (t, 1H), 8.54 (d, 1H), 8.49 (d, 1H), 8.05 (s, 1H), 8.00 (t, 1H), 7.70 (s, 1H), 7.60 (d, 1H), 7.40 (d, 1H), 4.90 (d, 1H).\",\"reactant_000\":\"NC(=O)c1cccc2c(O)nnnc12\",\"reactant_002\":null,\"reactant_001\":\"NCc1ccc(Cl)c(Cl)c1\",\"rxn_time\":null,\"reactant_003\":null,\"similarity\":0.9905708432197571,\"agent_000\":null,\"agent_001\":null,\"agent_002\":null,\"temperature\":null,\"product_000\":\"NC(=O)c1cccc2c(NCc3ccc(Cl)c(Cl)c3)nnnc12\",\"rxn_str\":\"[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[Cl:8].O[C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][NH:10][C:12]1[C:13]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH2:24])=[O:23])[C:14]=2[N:15]=[N:16][N:17]=1\",\"yield_000\":null}]","literatureScore":0.99,"label":"CF T5 AT UA ER TTL LR ALL ALL>>159","id":159},"children":[{"depth":8,"reaction":{"label":"T5 AT UA ER TTL ALL>>463","id":463},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"VTUAEMSZEIGQRM","smiles":"OC1=NC=NC2=C1C=C(C(F)=C2)[N+]([O-])=O","intrinsicScore":0.32,"id":463,"pathId":1722}]},{"depth":8,"reaction":{"label":"TTL ALL>>19","id":19},"molecules":[{"energyScore":0,"commercial":true,"industrialScore":0,"inchi":"YSEMCVGMNUUNRK","smiles":"NC1=CC=C(F)C(Cl)=C1","intrinsicScore":0.051,"id":19,"pathId":1722}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CJOJDNRJDBWZKM","smiles":"[O-][N+](=O)C1=CC2=C(C=C1F)N=CN=C2NC1=CC(Cl)=C(F)C=C1","intrinsicScore":0.3,"id":159,"pathId":1722}],"RXN":"[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH2:20])[Cl:23])[F:16].[cH:14]1[c:9]2[c:8]([cH:7][c:5]([c:4]1[N+:1](=[O:2])[O-:3])[F:6])[n:13][cH:12][n:11][c:10]2O>>[cH:18]1[cH:17][c:15]([c:22]([cH:21][c:19]1[NH:20][c:10]2[c:9]3[cH:14][c:4]([c:5]([cH:7][c:8]3[n:13][cH:12][n:11]2)[F:6])[N+:1](=[O:2])[O-:3])[Cl:23])[F:16];1.2.9;Alcohol"},{"depth":7,"reaction":{"label":"CF T5 AT ER UA TTL ALL>>522","id":522},"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"GDTBXPJZTBHREO","smiles":"BrBr","intrinsicScore":0.3,"id":522,"pathId":1722}]}],"molecules":[{"energyScore":0,"commercial":false,"industrialScore":0,"inchi":"CUHXEXBIVQEVJM","smiles":"[O-][N+](=O)C1=CC2=C(N=CN=C2NC2=CC(Cl)=C(F)C=C2)C(Br)=C1F","intrinsicScore":0.33,"id":528,"pathId":1722}],"RXN":"[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([cH:11][c:3]3[n:2][cH:1][n:23]2)[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22].[Br:24]Br>>[cH:21]1[cH:20][c:19]([c:17]([cH:16][c:15]1[NH:14][c:13]2[c:4]3[cH:5][c:6]([c:10]([c:11]([c:3]3[n:2][cH:1][n:23]2)[Br:24])[F:12])[N+:7](=[O:9])[O-:8])[Cl:18])[F:22];10.1.1;Bromination"},{"depth":6,"reaction":{"label":"UA 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