Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([N+:11]([O-])=O)=[CH:4][N:3]=1>CO>[ClH:1].[NH2:8][C:7]1[CH:2]=[N:3][CH:4]=[C:5]([NH2:11])[CH:6]=1
Reactant: O=[N+]([O-])c1cnc(Cl)c([N+](=O)[O-])c1
Solvent: CO
Product: Cl
Product: Nc1cncc(N)c1
Temperature: 0 °C
Yield: 124 %

Procedure:
2-chloro-3,5-dinitro-pyridine (27.36 g, 1) was divided into two equal portions and added into two 2 L round bottomed flasks. Methanol (700 mL) was then added to each flask. Nitrogen gas was bubbled through the solution while stirring and 7.15 g of 10% palladium on carbon was divided into two equal portions and added to each flask portion-wise under nitrogen. The solutions were cooled down under N2 to 0° C. using an ice-water bath. The N2 inlets were then replaced by hydrogen balloons. After evacuation, the solutions were exposed to H2 gas at slightly positive pressure. This vacuum-hydrogen exchange was done at least 5 times. The reactions were stirred under slight positive pressure of H2 for 2 days. Then the solutions were filtered with suction through Celite to remove the catalyst. The filtrate was concentrated down in vacuo. The crude product (24.27 g, >100% crude yield) was obtained as a dark green solid that was immediately used directly in the next step without further purification. The identity of the product (2) was confirmed by LC-MS.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:16]3[N:17]([C:30]([CH3:33])=[N:31][N:32]=3)[N:18]=[C:19]([C:21]3[NH:22][C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:16]3[N:17]([C:30]([CH3:33])=[N:31][N:32]=3)[N:18]=[C:19]([C:21]3[N:22]([CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: BrCc1ccccc1
Reactant: Cc1nnc2c(NC3CCN(C(=O)OC(C)(C)C)CC3)cc(-c3cc4ccccc4[nH]3)nn12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1nnc2c(NC3CCN(C(=O)OC(C)(C)C)CC3)cc(-c3cc4ccccc4n3Cc3ccccc3)nn12
Reaction time: 16 h

Procedure:
4-[6-(1H-Indol-2-yl)-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino]-piperidine-1-carboxylic acid tert-butyl ester (71.00 mg; 0.16 mmol) was suspended in 300 μl THF and treated with NaH (10.19 mg; 0.26 mmol; 60% in mineral oil). After 10 minutes of stilling, Benzyl bromide (19.17 μl; 0.16 mmol) was added and stirred for 16 hours. The crude material was purified via flash chromatography and afterwards with reversed phase chromatography under basic conditions.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([CH3:24])[CH:23]=1)[C:5]([N:7]1[CH2:12][CH2:11][NH:10][CH:9]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH2:8]1)=[O:6].CCN(C(C)C)C(C)C.[Br:34][CH2:35][C:36](Br)=[O:37]>C(Cl)Cl>[Br:34][CH2:35][C:36]([N:10]1[CH2:11][CH2:12][N:7]([C:5](=[O:6])[C:4]2[CH:21]=[C:22]([CH3:24])[CH:23]=[C:2]([CH3:1])[CH:3]=2)[CH2:8][CH:9]1[C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=1)=[O:37]
Reactant: Cc1cc(C)cc(C(=O)N2CCNC(c3ccc(Cl)c(Cl)c3)C2)c1
Reactant: O=C(Br)CBr
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cc(C)cc(C(=O)N2CCN(C(=O)CBr)C(c3ccc(Cl)c(Cl)c3)C2)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 46.3 %

Procedure:
To a cooled solution of (±)-[3,5-dimethylbenzoyl]-3-(3,4-dichlorophenyl)piperazine (11.5 g, 31.65 mmol) in CH2Cl2 (200 mL) at 0° C. was added Hunig's base (4.5 g, 35 mmol) and bromoacetyl bromide (6.4 g, 31.65 mmol). The solution was stirred at 0° C. overnight under N2. After completion the reaction was diluted with CH2Cl2 (400 mL) and washed with brine (300 mL, 2×), dried over MgSO4, filtered and concentrated. The crude material was purified by flash grade silica gel chromatography, eluting with 2% [NH4OH/MeOH (1:9)]/98% CH2Cl2 to give the title compound as a light yellow solid (7.1 g, 47.3%), m.p. 77-79° C., FAB MS [M+1]+35Cl, 79Br 482.9, 484.9.
Reaction SMILES: [CH3:1][CH:2]([CH2:6][CH2:7]/[CH:8]=[C:9](\[CH3:21])/[CH2:10][CH2:11]/[CH:12]=[C:13](\[CH3:20])/[CH2:14][CH2:15][CH:16]=[C:17]([CH3:19])[CH3:18])[CH2:3][C:4]#N.[OH-:22].[K+].C(O)C([OH:27])C.Cl>O>[CH3:1][CH:2]([CH2:6][CH2:7]/[CH:8]=[C:9](\[CH3:21])/[CH2:10][CH2:11]/[CH:12]=[C:13](\[CH3:20])/[CH2:14][CH2:15][CH:16]=[C:17]([CH3:19])[CH3:18])[CH2:3][C:4]([OH:27])=[O:22]
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/CCC(C)CC#N
Reactant: [OH-]
Reactant: CC(O)CO
Agent: Cl
Agent: [K+]
Solvent: O
Product: CC(C)=CCC/C(C)=C/CC/C(C)=C/CCC(C)CC(=O)O

Procedure:
To 34 g. of the product obtained in the above (b) step, there were added 23 g. of potassium hydroxide, 10 ml. of water and 70 ml. of propylene glycol, and the mixture was stirred at 130° C. for 7 hours. The reaction mixture was made acidic by addition of hydrochloric acid, and was then extracted with n-hexane. The extract was washed with water and dried, and the solvent was removed by evaporation. The residue was purified by silica gel column chromatography to obtain 30 g. of the desired oily product.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12](=[O:23])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=1.[C:24](Cl)(=[O:29])[CH2:25][CH:26]([CH3:28])[CH3:27]>>[Cl:11][C:7]1[CH:6]=[C:5]2[C:10]([C:2]([NH:1][C:24](=[O:29])[CH2:25][CH:26]([CH3:28])[CH3:27])=[C:3]([C:12](=[O:23])[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)[NH:4]2)=[CH:9][CH:8]=1
Reactant: Nc1c(C(=O)c2cccc(C(F)(F)F)c2)[nH]c2cc(Cl)ccc12
Reactant: CC(C)CC(=O)Cl
Product: CC(C)CC(=O)Nc1c(C(=O)c2cccc(C(F)(F)F)c2)[nH]c2cc(Cl)ccc12

Procedure:
The title compound was prepared according to the procedure described in Example 19 employing 3-amino-6-chloro-2-(3-trifluoromethylbenzoyl)indole (Example 49) and isovaleryl chloride. m.p.: 179-180° C.
Reaction SMILES: [OH:1][C:2]1[CH2:7][C:6]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(CCC2C=CC=CC=2)[O:5][C:4](=[O:22])[CH:3]=1.C1C(=O)N(Br)C(=O)C1.[CH:31]([N:34]1[CH2:39][CH2:38][CH2:37][NH:36][C:35]1=[S:40])([CH3:33])[CH3:32].N1CCCCC1>C(Cl)Cl.C(O)(C)(C)C>[OH:1][C:2]1[CH2:7][CH:6]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[O:5][C:4](=[O:22])[C:3]=1[S:40][C:35]1[N:34]([CH:31]([CH3:33])[CH3:32])[CH2:39][CH2:38][CH2:37][N:36]=1
Reactant: O=C1C=C(O)CC(CCc2ccccc2)(c2ccccc2)O1
Reactant: CC(C)N1CCCNC1=S
Agent: O=C1CCC(=O)N1Br
Solvent: ClCCl
Solvent: CC(C)(C)O
Solvent: C1CCNCC1
Product: CC(C)N1CCCN=C1SC1=C(O)CC(c2ccccc2)OC1=O

Procedure:
The title compound was prepared as described in example 41 using the following: 5, 6-dihydro-4-hydroxy-6-phenyl-6-(2-phenylethyl)-2H-pyran-2-one (0.250 g, 0.850 mmol), t-butanol (3.5 mL), n-bromosuccinimide (0.151 g, 0.85 mmol), CH2Cl2 (6.0 mL), 1-isopropyltetrahydropyrimidine-2-thione (0.270 g, 1.70 mmol, prepared by the method described by A. F. McKay et al., J. Am. Chem. Soc. 78:1618 (1956)), piperidine (0.084 mL, 0.85 mmol). Purification was achieved by submitting the final residue to column chromatograpy (SiO2, 1/1 CH2Cl2 /ethyl acetate to 2/14/1 ethyl acetate/CH2Cl2 /methanol) to provide a solid which was redissolved in CH2Cl2, filtered through a fiberglass filter, and the solvent removed in vacuo to provide the title compound (0.356 g, m.p. 103-105° C.). 1H NMR (400 MHz, DMSO-d6) δ 7.440-7.371 (m, 4 H), 7.296 (t, 1 H, J=7 Hz), 7.233 (t, 2 H, J=7 Hz), 7.139 (t, 1 H, J=7 Hz), 7.077 (d, 2 H, J=7 Hz), 6.515 (bs, 1 H), 4.365-4.300 (m, 1 H), 3.335-3.308 (m, 2 H), 3.024-2.924 (m, 4 H), 2.624-2.548 (m, 1 H), 2.341-2.265 (m, 1 H), 2.156-2.061 (m, 2 H), 1.763-1.737 (m, 2 H), 1.201-1.180 (m, 6 H).