Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH:7]12[CH2:13][CH:10]([CH2:11][CH2:12]1)[CH2:9][CH:8]2[CH2:14][NH:15][C:16](=[O:24])[C:17]1[CH:22]=[CH:21][CH:20]=[N:19][C:18]=1[SH:23].Br[CH2:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1.CCCCCC.CC(=O)OCC>CN(C=O)C>[CH:10]12[CH2:13][CH:7]([CH:8]([CH2:14][NH:15][C:16]([C:17]3[C:18]([S:23][CH2:26][CH2:27][CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)=[N:19][CH:20]=[CH:21][CH:22]=3)=[O:24])[CH2:9]1)[CH2:12][CH2:11]2
Reactant: Fc1ccc(CCCBr)cc1
Reactant: O=C(NCC1CC2CCC1C2)c1cccnc1S
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: O=C(NCC1CC2CCC1C2)c1cccnc1SCCCc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 70.3 %

Procedure:
178 mg (1.29 mmol) of K2CO3 were added to a solution of 308 mg (1.18 mmol) of N-(bicyclo[2.2.1]heptan-2-ylmethyl)-2-mercapto-nicotinamide in DMF (5 ml), and the mixture was stirred for 60 min at RT. 255 mg (1.18 mmol) of 1-(3-bromopropyl)-4-fluorobenzene were then added and the mixture was stirred for a further 16 h at RT. Dilution with water and extraction with EA were then carried out. The organic phase was washed with water, dried over MgSO4, filtered and concentrated in vacuo. CC (hexane/EA 2:1) of the residue yielded 333 mg (0.83 mmol, 71%) of N-(5-bicyclo-[2.2.1]heptanyl-methyl)-2-[3-(4-fluorophenyl)-propyl-sulfanyl]-pyridine-3-carboxylic acid amide. MS: m/z 399.2 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[C:3]2[C:4]3[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]=3[CH:12]=[CH:13][CH:14]=2.C([O-])([O-])=O.[K+].[K+].[F:21][C:22]([F:28])([F:27])[CH2:23][CH2:24][CH2:25]I.O>CN(C)C=O>[Br:1][C:2]1[C:3]2[C:4]3[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:25][CH2:24][CH2:23][C:22]([F:28])([F:27])[F:21])[C:6](=[O:11])[C:5]=3[CH:12]=[CH:13][CH:14]=2
Reactant: FC(F)(F)CCCI
Reactant: O=C1Nc2ccc(Br)c3cccc1c23
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1c2cccc3c(Br)ccc(c23)N1CCCC(F)(F)F
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 85.5 %

Procedure:
To a solutiion of 6-bromo-benzo[cd]indol-2(1H)-one (1 g, 4 mmol) in N,N-dimethyl formamide was added K2CO3 (5.53 g, 40 mmol) and the resulting mixture was stirred for 0.5 hour under nitrogen. 4,4,4-trifluorobutyl iodide (915 mg, 4 mmol ) was next injected to the solution and the mixture was heated at 60° C. for 18 hours. The reaction media was next poured into 200 ml water and extracted with trichloromethane (3×100 ml). Column chromatography using gradient ethyl acetate in hexane (10˜20%) gave the desired product (1.225 g, 85%).
Reaction SMILES: [CH:1]1([C:4]2[C:5]([CH:18]([CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH2:19][C:20]([O-])=[O:21])=[N:6][O:7][C:8]=2[CH:9]2[CH2:12][CH:11]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:10]2)[CH2:3][CH2:2]1.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([NH2:36])=[C:32]([CH3:37])[CH:31]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(=O)(O)[O-].[Na+]>O.CN(C=O)C>[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:20]([CH2:19][CH:18]([C:5]2[C:4]([CH:1]3[CH2:3][CH2:2]3)=[C:8]([CH:9]3[CH2:12][CH:11]([CH2:13][C:14]([CH3:17])([CH3:15])[CH3:16])[CH2:10]3)[O:7][N:6]=2)[CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])=[O:21])=[C:32]([CH3:37])[CH:31]=1
Reactant: COC(=O)CCC(CC(=O)[O-])c1noc(C2CC(CC(C)(C)C)C2)c1C1CC1
Reactant: Cc1cc(Cl)ccc1N
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)CCC(CC(=O)Nc1ccc(Cl)cc1C)c1noc(C2CC(CC(C)(C)C)C2)c1C1CC1
Temperature: 25 °C
Yield: 55.2 %

Procedure:
6-Methyl 3-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}adipate (100 mg), 4-chloro-2-methylphenylamine (43.5 mg) and DMF (1 mL) were mixed. To the mixture were added HOBt.H2O (47 mg) and WSC.HCl (58.8 mg) at ice temperature. The mixture was stirred at RT, and further stirred at 70° C. To the reaction mixture was added saturated aqueous sodium bicarbonate at ice temperature. The mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by preparative chromatography (Eluent: ethyl acetate/hexane=1/4) to give the title compound (72.8 mg).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15](CC3C=CC(OC)=CC=3OC)[C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[C:5]([OH:32])=[CH:4][N:3]=1.[CH3:33][O:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=1B(O)O>>[OH:32][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])[CH:7]=2)[C:2]([C:36]2[CH:37]=[CH:38][C:39]([C:41]([F:44])([F:43])[F:42])=[CH:40][C:35]=2[O:34][CH3:33])=[N:3][CH:4]=1
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(Cl)ncc(O)c3c2)c(OC)c1
Reactant: COc1cc(C(F)(F)F)ccc1B(O)O
Product: COc1cc(C(F)(F)F)ccc1-c1ncc(O)c2cc(S(=O)(=O)Nc3nccs3)ccc12

Procedure:
Example 232 was synthesized in a similar manner to Example 228, except that 1-chloro-N-(2,4-dimethoxybenzyl)-4-hydroxy-N-(thiazol-2-yl)isoquinoline-6-sulfonamide and (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid were used as the coupling partners. The final compound was purified via column chromatography (12 g silica gel column, gradient elution 0 to 5% MeOH:DCM) to afford 4-hydroxy-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=12.89 (s, 1H), 11.03 (s, 1H), 8.64 (d, J=1.4 Hz, 1H), 8.24 (s, 1H), 7.84 (dd, J=1.8, 8.9 Hz, 1H), 7.60 (d, J=8.9 Hz, 1H), 7.55-7.49 (m, 1H), 7.48-7.42 (m, 2H), 7.28 (d, J=4.6 Hz, 1H), 6.86 (d, J=4.5 Hz, 1H), 3.73 (s, 3H). m/z (ESI) 482.2 (M+H)+.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[N:9]([CH3:10])[C:8]2[S:11][CH:12]=[CH:13][C:7]=2[CH:6]=1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:10][N:9]1[C:5]([CH2:3][NH:2][CH3:1])=[CH:6][C:7]2[CH:13]=[CH:12][S:11][C:8]1=2
Reactant: CNC(=O)c1cc2ccsc2n1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CNCc1cc2ccsc2n1C
Temperature: 25 °C
Yield: 114.2 %

Procedure:
To a solution of N,6-dimethyl-6H-thieno[2,3-b]pyrrole-5-carboxamide (134 mg, 0.69 mmole) in dry THF (5 mL) was added a solution of LiAlH4 in THF (1.0 M, 1.38 mL, 1.38 mmole) slowly at RT. After gas evolution had ceased the mixture was heated to a gentle reflux. After 2 hr the mixture was cooled to RT and quenched by dropwise addition of 2M NaOH until a white solid had formed. The mixture was dried (MgSO4), filtered, and concentrated to give the title compound as a brown oil (142 mg, 100%) which was sufficiently pure for use in the next step: 1H NMR (400 MHz, CDCl3) δ 6.95 (d, J=5.2 Hz, 1H), 6.78 (d, J=5.2 Hz, 1H), 6.27 (s, 1H), 3.78 (s, 2H), 3.72 (s, 3H), 2.47 (s, 3H).
Reaction SMILES: [CH3:1][O:2][P:3]([C:7]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:8]=1[CH2:9][NH:10]C(=O)OC(C)(C)C)([O:5][CH3:6])=[O:4].[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26]>ClCCl>[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26].[NH2:10][CH2:9][C:8]1[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:7]=1[P:3](=[O:4])([O:5][CH3:6])[O:2][CH3:1]
Reactant: COP(=O)(OC)c1cc(F)ccc1CNC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COP(=O)(OC)c1cc(F)ccc1CN
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of tert-butyl 2-(dimethoxyphosphoryl)-4-fluorobenzylcarbamate (0.140 g, 0.42 mmol) in dichloromethane (5 ml) was treated with trifluoroacetic acid (5 ml) and the resulting mixture was stirred at 25° C. for 1 h. The solvent was then evaporated in vacuo to give the title amine salt as an amorphous white solid. MS (ESI+) m/z 234 [M+H+].
Reaction SMILES: Cl.NCC([C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11](=[O:15])[NH:12]2)=[CH:8][CH:7]=1)=O.[CH2:16]([CH:23]1[CH2:28][CH2:27][N:26]([CH2:29][C:30]([OH:32])=O)[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:16]([CH:23]1[CH2:24][CH2:25][N:26]([CH2:29][C:30]([NH:26][CH2:29][C:30](=[O:32])[C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:6]=2)[NH:12][C:11](=[O:15])[CH2:10]3)=[O:32])[CH2:27][CH2:28]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: NCC(=O)c1ccc2c(c1)NC(=O)C2
Reactant: O=C(O)CN1CCC(Cc2ccccc2)CC1
Agent: Cl
Product: O=C(CN1CCC(Cc2ccccc2)CC1)NCC(=O)c1ccc2c(c1)CC(=O)N2

Procedure:
Condensation of 6-(2-aminoethanoyl)-1,3-dihydroindol-2-one hydrochloride with (4-benzylpiperidin-1-yl)acetic acid, following the procedure described in Example 6, Step 6, gave 2-(4-benzyl-piperidin-1-yl)-N-[2-oxo-2-(2-oxo-2,3-dihydro-1H-indol-5-yl)ethyl]acetamide:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH2:16]I)=[CH:11][C:10]=1[NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([NH2:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[CH2:31]([NH:38][CH2:16][C@@H:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:10]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:11]=1)[O:18][Si:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: NCc1ccccc1
Reactant: CC[Si](CC)(CC)O[C@@H](CI)c1ccc(OCc2ccccc2)c(NS(C)(=O)=O)c1
Product: CC[Si](CC)(CC)O[C@@H](CNCc1ccccc1)c1ccc(OCc2ccccc2)c(NS(C)(=O)=O)c1
Temperature: 65 °C
Reaction time: 22 h

Procedure:
N-[2-benzyloxy-5-((1R)-2-iodo-1-triethylsilanyloxy-ethyl)-phenyl]-methanesulfonamide (0.56 g, 1 mmol) was dissolved in benzylamine (0.54 g, 5 mmol) and stirred at 65° C. for 22 h.
Reaction SMILES: [OH:1][C:2]1[CH:14]=[CH:13][C:5]2[N:6]([CH3:12])[C:7](=[S:11])[CH:8]([CH3:10])[O:9][C:4]=2[CH:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([C:24]([F:27])([F:26])[F:25])[CH:19]=[C:20]([F:23])[C:21]=1F.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[Cl:15][C:16]1[CH:17]=[C:18]([C:24]([F:25])([F:26])[F:27])[CH:19]=[C:20]([F:23])[C:21]=1[O:1][C:2]1[CH:14]=[CH:13][C:5]2[N:6]([CH3:12])[C:7](=[S:11])[CH:8]([CH3:10])[O:9][C:4]=2[CH:3]=1
Reactant: CC1Oc2cc(O)ccc2N(C)C1=S
Reactant: Fc1cc(C(F)(F)F)cc(Cl)c1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CC1Oc2cc(Oc3c(F)cc(C(F)(F)F)cc3Cl)ccc2N(C)C1=S
Temperature: 80 °C
Reaction time: 1 h

Procedure:
First, 7-hydroxy-2,4-dimethyl-2H-1,4-benzoxazine-3 (4H)-thione (0.2 g) and 3-chloro-4,5-difluorotrifluoromethylbenzene (0.3 g) were dissolved in DMSO (5 ml), potassium carbonate (0.2 g) was added thereto, and the mixture was stirred at 80° C. for one hr. Water (10 ml) was added thereto to terminate the reaction, and the reaction mixture was extracted with ethyl acetate (20 ml×2), washed with water and a saturated saline solution and dried over anhydrous magnesium sulfate. The solvent was distilled off in vacuo, and the residue was purified by silica gel chromatography (developing solvent: n-hexane/ethyl acetate=5/1) to prepare the title compound (0.2 g) as a colorless crystal.