Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Li]CCCC.CC1(C)CCCC(C)(C)N1.[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([OH:22])=[O:21].O=[C:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1>C1COCC1>[Cl:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:19]2[C:18]=1[C:27]1([CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1)[O:21][C:20]2=[O:22]
Reactant: O=C(O)c1cccc(Cl)c1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC1(C)CCCC(C)(C)N1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC2(CC1)OC(=O)c1cccc(Cl)c12
Temperature: -20 °C
Reaction time: 1 h
Yield: 12.9 %

Procedure:
2.5 M n-BuLi in hexanes (9.2 mL, 23 mmol) was added To a stirred solution of 2,2,6,6-tetramethylpiperidine (3.2 g, 23 mmol) in anhydrous THF (30 mL) at −20° C. under N2. The mixture was stirred for 1 h. at −20° C. and then cooled to −78° C. 3-Chlorobenzoic acid (1.8 g, 11.5 mmol) in anhydrous THF (20 mL) was slowly added dropwise and the mixture was stirred for 1 h at −78° C. The mixture was treated with tert-butyl 4-oxopiperidine-1-carboxylate (2.29 g, 11.5 mmol) and the resulting solution was warmed to rt and stirred overnight. The mixture was quenched with water and extracted with EtOAc (3×30 mL). The organic layers were combined, washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product, which was Purified by chromatography to give tert-butyl 7-chloro-3-oxo-3H-spiro[isobenzofuran-1,4′-piperidine]-1′-carboxylate (500 mg, 13%). 1H NMR (CD3OD): δ=1.45 (s, 9H), 2.60 (m, 2H), 3.20 (b, 2H), 4.20 (b, 2H), 7.48 (m, 1H), 7.55 (m, 1H), 7.75 (m, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([CH3:28])[C:14]2[C:9](=[CH:10][C:11]([NH:18][C:19]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[O:20])=[C:12]([N+:15]([O-])=O)[CH:13]=2)[NH:8][C:7]1=[O:27])=[O:5])[CH3:2]>[Pd].CO>[NH2:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[NH:18][C:19]([C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1)=[O:20])[NH:8][C:7](=[O:27])[C:6]2([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH3:28]
Reactant: CCOC(=O)C1(C)C(=O)Nc2cc(NC(=O)c3ccncc3)c([N+](=O)[O-])cc21
Agent: [Pd]
Solvent: CO
Product: CCOC(=O)C1(C)C(=O)Nc2cc(NC(=O)c3ccncc3)c(N)cc21

Procedure:
A solution of 12.4 g. (32.2 mmol) 3-ethoxycarbonyl-3-methyl-5-nitro-6-(4-pyridinoylamino)-indolin-2-one in 500 ml. methanol is hydrogenated at ambient temperature in the presence of 1 g. 10% Pd/C. The catalyst is filtered off with suction, the filtrate is evaporated and the substance obtained is immediately further worked up.
Reaction SMILES: C(P(CCCC)CCCC)CCC.[CH3:14][C:15]1[C:20]([CH2:21][OH:22])=[CH:19][CH:18]=[C:17]([C:23]([F:26])([F:25])[F:24])[N:16]=1.[CH3:27][O:28][C:29](=[O:43])[CH2:30][C:31]1[C:35]2[C:36]([CH3:42])=[CH:37][C:38](O)=[C:39]([CH3:40])[C:34]=2[S:33][CH:32]=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[CH3:27][O:28][C:29](=[O:43])[CH2:30][C:31]1[C:35]2[C:36]([CH3:42])=[CH:37][C:38]([O:22][CH2:21][C:20]3[C:15]([CH3:14])=[N:16][C:17]([C:23]([F:24])([F:26])[F:25])=[CH:18][CH:19]=3)=[C:39]([CH3:40])[C:34]=2[S:33][CH:32]=1
Reactant: COC(=O)Cc1csc2c(C)c(O)cc(C)c12
Reactant: Cc1nc(C(F)(F)F)ccc1CO
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: COC(=O)Cc1csc2c(C)c(OCc3ccc(C(F)(F)F)nc3C)cc(C)c12
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.8 %

Procedure:
To a mixture of tri-n-butylphosphine (0.196 mL), (2-methyl-6-(trifluoromethyl)pyridin-3-yl)methanol (105 mg), methyl(6-hydroxy-4,7-dimethyl-1-benzothiophen-3-yl)acetate (130.9 mg) and THF (5.0 mL) was added ADDP (198 mg) at room temperature. The mixture was stirred at room temperature overnight under nitrogen atmosphere. The mixture was concentrated in vacuo. To the residue was added IPE, and the precipitate was filtered off. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (159 mg) as solid. The solid was crystallized from EtOAc-hexane.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5](=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[NH:15][C:14]1=[O:22].[Cl:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27]Cl>CN(C=O)C>[CH3:3][O:4][C:5](=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N:15]([CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[CH:32][C:25]=2[Cl:24])[C:14]1=[O:22]
Reactant: ClCc1ccccc1Cl
Reactant: COC(=O)CCCCCCCn1c(=O)[nH]c2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)CCCCCCCn1c(=O)n(Cc2ccccc2Cl)c2ccccc21

Procedure:
The product is produced as described in example 1 from 0.72 g. of NaH (80% suspension in mineral oil), 7 g. of 8-(2-oxobenzimidazolin-1-yl)-caprylic acid methyl ester, 100 cc. of DMF, 3.9 g. of 2-chlorobenzylchloride and 0.72 g. of NaJ. Eluant of chromatographic purification: hexane/ethylacetate.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[CH:17]=[CH:16][CH:15]=[C:14]4[CH2:19][NH:20][CH2:21][CH2:22][C:12]([C:13]=34)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[C:25](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>COCCOC>[CH3:25][N:20]1[CH2:21][CH2:22][C:12]2=[CH:11][N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:9])=[O:8])[C:18]3[CH:17]=[CH:16][CH:15]=[C:14]([C:13]=32)[CH2:19]1
Reactant: O=S(=O)(c1ccccc1)n1cc2c3c(cccc31)CNCC2
Reactant: CC(=O)O
Agent: C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: COCCOC
Product: CN1CCc2cn(S(=O)(=O)c3ccccc3)c3cccc(c23)C1
Temperature: 25 °C

Procedure:
1-(Phenylsulfonyl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol, Example 15 (34.4 mg, 0.11 mmol) was dissolved in DME (2 mL) and added formaldehyde (37% Wt. solution in water, 0.1 mL, 1.1 mmol), acetic acid (0.05 mL, 0.7 mmol) and sodium triacetoxyborohydride (156 mg, 0.7 mmol). The reaction mixture was stirred at room temperature for 24 H. The reaction was quenched by adding 1 M NaOH (5 mL). Aqueous phase (pH about 14) was separated and was then extracted with DCM (3×5 mL). The combined organic phases was washed with water and brine, and dried with MgSO4. The solvent was removed under vacuum. 20 mg pure product was obtained as an off-white solid. MS m/z 327 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH:11]([N:13]3[CH:17]=[N:16][CH:15]=[N:14]3)[CH3:12])[CH2:10][O:9]2)=[N:6][CH:7]=1.[NH:18]1[CH:22]=[N:21][CH:20]=[N:19]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[N:18]1([CH2:10][C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)([OH:9])[CH:11]([N:13]2[CH:17]=[N:16][CH:15]=[N:14]2)[CH3:12])[CH:22]=[N:21][CH:20]=[N:19]1
Reactant: c1nc[nH]n1
Reactant: CC(n1cncn1)C1(c2ccc(Cl)cn2)CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(n1cncn1)C(O)(Cn1cncn1)c1ccc(Cl)cn1
Reaction time: 3 h
Yield: 28.1 %

Procedure:
To a solution of 2-[5-chloropyrid-2-yl]-2-[1-(1H-1,2,4-triazol-1-yl)ethyl]oxirane (70 mg; 0.28 m.Mole) in dimethylformamide (5 ml) was added 1,2,4-triazole (39 mg; 0.56 m.Mole) and anhydrous potassium carbonate (39 mg; 0.28 m.Mole). Heating, with stirring, was carried out for three hours at 80°. The solvent was then evaporated, water (20 ml.) was added, and the mixture was extracted with methylene chloride (3×10 ml). The combined organic extracts were washed with water (3×5 ml), dried over anhydrous magnesium sulphate, and evaporated to an oil (100 mg). Purification was carried out using a flash column of Merck "Kieselgel 60" 230-400 mesh silica, eluting with methylene chloride containing gradually increasing amounts of methanol (from 1 to 5%). The appropriate fractions, on evaporation, gave the pure title compound, 25 mg; m.p. 156°-157° (28.1% yield).
Reaction SMILES: [C:1]1([CH:7]([C:16]2[CH:21]=[CH:20][C:19](B3OC(C)(C)C(C)(C)O3)=[CH:18][CH:17]=2)[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:32]1[C:40]2[C:35](=[N:36][CH:37]=[N:38][C:39]=2[NH2:41])[N:34]([C@H:42]2[CH2:47][CH2:46][C@@H:45]([N:48]3[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]3)[CH2:44][CH2:43]2)[N:33]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[NH2:41][C:39]1[N:38]=[CH:37][N:36]=[C:35]2[N:34]([C@H:42]3[CH2:47][CH2:46][C@@H:45]([N:48]4[CH2:49][CH2:50][N:51]([CH3:54])[CH2:52][CH2:53]4)[CH2:44][CH2:43]3)[N:33]=[C:32]([C:19]3[CH:18]=[CH:17][C:16]([CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:21][CH:20]=3)[C:40]=12
Reactant: CN1CCN([C@H]2CC[C@@H](n3nc(I)c4c(N)ncnc43)CC2)CC1
Reactant: CC(C)(C)OC(=O)NC(c1ccccc1)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CN1CCN([C@H]2CC[C@@H](n3nc(-c4ccc(C(NC(=O)OC(C)(C)C)c5ccccc5)cc4)c4c(N)ncnc43)CC2)CC1
Temperature: 25 °C
Yield: 69.4 %

Procedure:
A mixture of tert-butyl N-{phenyl[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}carbamate (3.0 g, 0.00733 mol), cis-3-iodo-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.4 g, 0.0054 mol), tetrakis-(triphenylphosphine)palladium (0.381 g, 0.00033 mol) and sodium carbonate monohydrate (1.69 g, 0.0136 mol) was heated in a mixture of ethylene glycol dimethyl ether (80 mL) and water (40 mL) at 80° C. for sixteen hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under the reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution (200 mL) and ethyl acetate (200 mL), the organic layer separated and the aqueous layer further extracted with ethyl acetate twice (100 mL each). The combined organic extracts were dried over magnesium sulfate. The solvents were evaporated under reduced pressure to leave a tan solid which was purified by flash column chromatography on silica using dichloromethane/triethylamine/methanol (96:3:1) as a mobile phase to give cis-tert-butyl N-[(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)(phenyl)-methyl]carbamate (2.24 g, 0.00375 mol) as a white solid.