Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([CH2:19][CH2:20][CH:21]2[O:26][CH2:25][CH2:24][CH2:23][O:22]2)[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1.[OH-].[NH4+:28]>CC(O)C>[O:22]1[CH2:23][CH2:24][CH2:25][O:26][CH:21]1[CH2:20][CH2:19][C:4]1[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=[C:2]([NH2:28])[N:3]=1
Reactant: Fc1ccc(-c2ccc3nc(Cl)nc(CCC4OCCCO4)c3n2)cc1
Reactant: [NH4+]
Agent: [OH-]
Solvent: CC(C)O
Product: Nc1nc(CCC2OCCCO2)c2nc(-c3ccc(F)cc3)ccc2n1
Temperature: 100 °C
Yield: 70 %

Procedure:
A suspension of 2-chloro-4-(2-[1,3]dioxan-2-yl-ethyl)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine (9 mg, 0.024 mmol) in iPrOH (0.5 mL) and 30% ammonium hydroxide (4 mL) was heated at 100° C. for 30 minutes. Solvents were concentrated in vacuo and the residue was purified by RP HPLC using a C18 column with a gradient of H2O and 0.1% TFA-acetonitrile, to provide the title compound as a white solid (6 mg, yield: 70%). The resulting title compound was characterised as follows: MS (m/z) 355.0 [M+H]+; HPLC Rt=3.34 minutes (Method A).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:15][C:16]([NH2:18])=[S:17])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1)#[N:2].Br[CH:20]1[CH2:25][CH2:24][CH2:23][CH:22]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21]1=O>C(O)C>[CH3:14][C:12]1[N:11]=[CH:10][N:9]([C:8]2[CH:7]=[CH:6][C:5]([NH:15][C:16]3[S:17][C:28]4[CH2:29][CH2:30][CH2:31][CH:26]([C:22]5[CH:23]=[CH:24][CH:25]=[CH:20][CH:21]=5)[C:27]=4[N:18]=3)=[CH:4][C:3]=2[C:1]#[N:2])[CH:13]=1
Reactant: O=C1C(Br)CCCC1c1ccccc1
Reactant: Cc1cn(-c2ccc(NC(N)=S)cc2C#N)cn1
Solvent: CCO
Product: Cc1cn(-c2ccc(Nc3nc4c(s3)CCCC4c3ccccc3)cc2C#N)cn1
Temperature: 25 °C
Yield: 87.5 %

Procedure:
A suspension of [3-cyano-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea (64.3 mg, 0.25 mmol) and of 2-bromo-6-phenyl-cyclohexanone (63.3 mg, 0.25 mmol) in ethanol (2 mL) was heated to reflux under an atmosphere of nitrogen for 2 days. After cooling to room temperature the solvent was evaporated under reduced pressure. The residue was suspended in dichloromethane/diethyl ether. The precipitated solid was filtered off, washed with diethyl ether and dried under reduced pressure to yield the title compound (90 mg, 88%) as a pale-brown solid. MS ISP (m/e): 412.2 (100) [(M+H)+]. 1H NMR (DMSO-D6, 300 MHz): δ (ppm)=10.75 (s, 1H), 9.31 (s, 1H), 8.16 (s, 1H), 7.78 (m, 2H), 7.65 (d, 1H), 7.30 (t, 2H), 7.17 (m, 3H), 4.08 (m, 1H), 2.75 (m, 2H), 2.34 (s, 3H), 2.15 m, 2H), 1.76 (m, 2H).
Reaction SMILES: [NH3:1].Cl[C:3]1[N:12]2[N:13]=[C:14]([CH:16]3[CH2:20][CH2:19][CH2:18][O:17]3)[N:15]=[C:11]2[C:10]2[CH:9]=[C:8]([Cl:21])[CH:7]=[CH:6][C:5]=2[N:4]=1>[OH-].[NH4+]>[Cl:21][C:8]1[CH:7]=[CH:6][C:5]2[NH:4][C:3](=[NH:1])[N:12]3[N:13]=[C:14]([CH:16]4[CH2:20][CH2:19][CH2:18][O:17]4)[N:15]=[C:11]3[C:10]=2[CH:9]=1
Reactant: N
Reactant: Clc1ccc2nc(Cl)n3nc(C4CCCO4)nc3c2c1
Agent: [NH4+]
Agent: [OH-]
Product: N=c1[nH]c2ccc(Cl)cc2c2nc(C3CCCO3)nn12

Procedure:
Concentrated aqueous ammonium hydroxide (50 ml) in a stainless steel pressure vessel is saturated with gaseous ammonia at 0° and 5,9-dichloro-2-(2-tetrahydrofuryl)[1,2,4]triazolo[1,5-c]-quinazoline (1.22 g) added. The mixture is heated over six hours at an outside temperature of 150°, cooled and filtered. The precipitate is washed with water and dried under high vacuum to afford pure 9-chloro-5-imino-2-(2-tetrahydrofuryl)-5,6-dihydro-[1,2,4]triazolo[1,5-c]-quinazoline (0.45 g), mp 203°-206°. The starting material is prepared as follows:
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:12]=[C:13]([CH:18]([OH:30])[CH:19]2[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20]2)[CH:14]=[CH:15][C:16]=1[Cl:17].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:30][CH:18]([C:13]1[CH:14]=[CH:15][C:16]([Cl:17])=[C:11]([Cl:10])[CH:12]=1)[CH:19]1[CH2:20][N:21]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:22]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CC(C(O)c2ccc(Cl)c(Cl)c2)C1
Reactant: O=C(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CC(C(OC(=O)c2ccccc2)c2ccc(Cl)c(Cl)c2)C1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Benzoyl chloride (0.1 mL, 1.20 mmol) and DMAP (5 mg, 0.03 mmol) were slowly added to 15 mL of tertiary butyl 3-((3,4-dichlorophenyl)(hydroxy)methyl)azetidine-1-carboxylate (100 mg, 0.302 mmol) and triethylamine (0.07 mL, 0.482 mmol) dissolved in the distilled methylene chloride solution at 0° C., and the mixture was stirred at room temperature for one day. The reaction mixture was extracted with methylene chloride (3*30 mL), and the organic layer was washed with a 1 N HCl aqueous solution and distilled water once, respectively and dried over anhydrous magnesium sulfate. The solvent was removed by reduced pressure evaporation to obtain a colorless liquid, which was purified by flash chromatography (n-hexane:ethyl acetate (2:1, v/v)). The product was identified as a single compound by TLC (n-hexane:ethyl acetate (2:1, v/v)).
Reaction SMILES: Cl[C:2]1[C:3]([F:23])=[CH:4][C:5]2[C:6]([CH:22]=1)=[N:7][C:8]1[N:9]([CH:19]3[CH2:21][CH2:20]3)[CH:10]=[C:11]([C:16]([OH:18])=[O:17])[C:12](=[O:15])[C:13]=1[CH:14]=2.[CH2:24]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[CH3:25]>N1C=CC=CC=1>[CH:19]1([N:9]2[C:8]3[N:7]=[C:6]4[CH:22]=[C:2]([N:29]5[CH2:30][CH2:31][N:26]([CH2:24][CH3:25])[CH2:27][CH2:28]5)[C:3]([F:23])=[CH:4][C:5]4=[CH:14][C:13]=3[C:12](=[O:15])[C:11]([C:16]([OH:18])=[O:17])=[CH:10]2)[CH2:21][CH2:20]1
Reactant: CCN1CCNCC1
Reactant: O=C(O)c1cn(C2CC2)c2nc3cc(Cl)c(F)cc3cc2c1=O
Solvent: c1ccncc1
Product: CCN1CCN(c2cc3nc4c(cc3cc2F)c(=O)c(C(=O)O)cn4C2CC2)CC1
Yield: 27.2 %

Procedure:
1-Cyclopropyl-8-(4-ethyl-1-piperazinyl)-7-fluoro-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine-3-carboxylic acid is prepared under the conditions of Example 5 but starting from 2 g of 8-chloro-1-cyclopropyl-7-fluoro-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine-3-carboxylic acid and 2.74 g of 1-ethylpiperazine in 20 cm3 of pyridine. The pure product is isolated after a first recrystallization from 105 cm3 of ethanol containing 25% of dimethylformamide followed by a second recrystallization from 75 cm3 of ethanol containing 50% of dimethylformamide. 0.67 g of 1-cyclopropyl-8-(4-ethyl-1-piperazinyl)-7-fluoro-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine-3-carboxylic acid is obtained in the form of a yellow-green solid melting at 254° C.
Reaction SMILES: Cl.Cl.Cl.[C:4]([C:7]1[CH:31]=[CH:30][C:10]([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]([CH2:19][CH:20]([O:22][C:23]3[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][CH:24]=3)[CH3:21])[CH2:15][CH2:14]2)=[CH:9][CH:8]=1)([OH:6])=[O:5].[C:32](OC(=O)C)(=[O:34])[CH3:33]>>[C:4]([C:7]1[CH:8]=[CH:9][C:10]([CH2:11][CH2:12][N:13]2[CH2:14][CH2:15][N:16]([CH2:19][CH:20]([O:22][C:23]3[CH:24]=[CH:25][C:26]([NH:29][C:32]([CH3:33])=[O:34])=[CH:27][CH:28]=3)[CH3:21])[CH2:17][CH2:18]2)=[CH:30][CH:31]=1)([OH:6])=[O:5]
Reactant: CC(CN1CCN(CCc2ccc(C(=O)O)cc2)CC1)Oc1ccc(N)cc1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Product: CC(=O)Nc1ccc(OC(C)CN2CCN(CCc3ccc(C(=O)O)cc3)CC2)cc1

Procedure:
A mixture of 9.3 g. (18.9 mmole) 1-(4-carboxyphenethyl)-4-[2-(4-aminophenoxy)-propyl]-piperazine trihydrochloride and 50 ml. acetic anhydride is kept for 2 hours at 100° C. and then cooled. The precipitate obtained is filtered off with suction and recrystallised from acetic acid. There are obtained 8.2 g. (87% of theory) of the desired compound in the form of a dihydrochloride; m.p. 234°-235° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([CH2:14][CH2:15][N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:12][NH2:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].N[C:22]([O:24][CH2:25][CH3:26])=[O:23]>>[CH2:25]([O:24][C:22](=[O:23])[NH:13][CH2:12][CH:11]([C:5]1[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH2:14][CH2:15][N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH3:26]
Reactant: CCOC(N)=O
Reactant: CCN(CC)CCC(CN)c1ccc(OC)c(OC)c1
Product: CCOC(=O)NCC(CCN(CC)CC)c1ccc(OC)c(OC)c1

Procedure:
From 2-(3,4-dimethoxyphenyl)-4-diethylamino-butylamine in analogy to 3a. The urethane was further reacted in a crude state.
Reaction SMILES: Br[CH2:2][CH3:3].[OH:4][C:5]1[CH:6]=[C:7]([N:11]2[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)[CH:8]=[CH:9][CH:10]=1.C(=O)([O-])[O-].[K+].[K+].O>CC(C)=O>[CH2:2]([O:4][C:5]1[CH:6]=[C:7]([N:11]2[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]2)[CH:8]=[CH:9][CH:10]=1)[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc(O)c2)CC1
Reactant: CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CCOc1cccc(N2CCNCC2)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 46 %

Procedure:
Bromoethane (0.7 mL) was added to a mixture of 1,1-dimethylethyl 4-(3-hydroxyphenyl)-1-piperazinecarboxylate (Description 21, 500 mg, 1.8 mmol) and potassium carbonate (495 mg) in acetone (50 mL) and the mixture was heated under reflux for 13 h. The mixture was cooled, water (100 mL) was added and the mixture was extracted with ether (3×100 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (95:5). The residue was dissolved in dichloromethane (14 mL), cooled to 0° C. and trifluoroacetic acid (9 mL) was added. The mixture was stirred at 0° C. for 1 h., then allowed to warm to room temperature and saturated aqueous sodium bicarbonate solution (40 mL) was added. The mixture was extracted with dichloromethane, the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a pale brown solid (210 mg, 46%). 1H NMR (250 MHz, CDCl3) δ1.43 (3H, t, J 7.6 Hz), 3.65-3.82 (8H, m), 3.98-4.13 (2H, m), 6.84-6.91 (2H, m), and 7.34-7.40 (1H, m).