Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[NH2:6].[OH-].[Na+].Cl[C:15]([O:17][CH3:18])=[O:16].O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:6][C:15]([O:17][CH3:18])=[O:16])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: COC(=O)Cl
Reactant: COc1ccc(N)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: COC(=O)Nc1ccc(OC)c(OC)c1
Temperature: -5 °C
Reaction time: 1.5 h
Yield: 90.7 %

Procedure:
A solution of 15.3 g (0.1 mol) of 3,4-dimethoxyaniline in 60 mL of methylene chloride was treated with 55 mL of 2N sodium hydroxide. The reaction mixture was cooled to -5° C. and 7.4 mL (0.096 mol) of methyl chloroformate was added keeping the reaction temperature between 15°-25° C. The reaction was stirred 1.5 hr at 10°-20° C. and then 50 mL of water was added. The layers were separated and the aqueous layer was extracted with 4×100 mL of methylene chloride. The combined methylene chloride layers were dried over sodium sulfate and Darco treated. Evaporation gave a paste which was recrystallized from 10 mL of ethyl acetate and 10 mL of hexanes to give 18.4 g (98%) of the product, mp 83°-87° C. NMR (CDCl3) δ 3.75 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 6.63 (br s, 1H, NH), 6.73 (m, 2H, ArH), 7.13 (m, 1H, ArH).
Reaction SMILES: [C:1]([C:5]1[N:6]([CH2:31][C:32](=[O:36])[C:33]([OH:35])=[O:34])[C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([NH:14][C:15]([C:17]1([C:20]3[CH:30]=[CH:29][C:23]4[O:24][C:25]([F:28])([F:27])[O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]1)=[O:16])=[CH:9][CH:8]=2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[C:1]([C:5]1[N:6]([CH2:31][CH:32]([OH:36])[C:33]([OH:35])=[O:34])[C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([NH:14][C:15]([C:17]1([C:20]3[CH:30]=[CH:29][C:23]4[O:24][C:25]([F:28])([F:27])[O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]1)=[O:16])=[CH:9][CH:8]=2)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1cc2cc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)ccc2n1CC(=O)C(=O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)c1cc2cc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)ccc2n1CC(O)C(=O)O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 3-(2-tert-butyl-5-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-1H-indol-1-yl)-2-oxopropanoic acid (50 mg, 0.10 mmol) in MeOH (1 mL) was added NaBH4 (19 mg, 0.50 mmol) at 0° C. The mixture was stirred at room temperature for 15 min. The resulting mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc twice and the combined organic layers were washed with brine and dried over anhydrous MgSO4. After the removal of the solvent, the residue was taken up in DMSO and purified by preparative LC/MS to give 3-(2-tert-butyl-5-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-1H-indol-1-yl)-2-hydroxypropanoic acid. 1H NMR (400 MHz, CDCl3) δ 7.36 (s), 7.27-7.23 (m, 2H), 7.15-7.11 (m, 2H), 6.94 (d, J=8.5 Hz, 1H), 6.23 (s, 1H), 4.71 (s, 3H), 4.59 (q, J=10.3 Hz, 1H), 4.40-4.33 (m, 2H), 1.70 (d, J=1.9 Hz, 2H), 1.15 (q, J=4.0 Hz, 2H). 13C NMR (400 MHz, CDCl3) δ 173.6, 173.1, 150.7, 144.1, 143.6, 136.2, 135.4, 134.3, 131.7, 129.2, 129.0, 127.6, 126.7, 116.6, 114.2, 112.4, 110.4, 110.1, 99.7, 70.3, 48.5, 32.6, 30.9, 30.7, 16.8. MS (ESI) m/e (M+H+) 501.2.
Reaction SMILES: [Br:1][C:2]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:13].ClCCl.[C:17](N1C=CN=C1)(N1C=CN=C1)=[S:18]>>[Br:1][C:2]1[C:8]([C:9]([F:10])([F:11])[F:12])=[CH:7][C:5]([N:6]=[C:17]=[S:18])=[CH:4][C:3]=1[Cl:13]
Reactant: Nc1cc(Cl)c(Br)c(C(F)(F)F)c1
Reactant: S=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: FC(F)(F)c1cc(N=C=S)cc(Cl)c1Br
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 4-bromo-3-chloro-5-(trifluoromethyl)aniline (15 g, 54.7 mmol, Eq: 1.00) in dichloromethane (13.2 g, 10.0 ml, 155 mmol, Eq: 25.3) at 0, was added 1,1′-thiocarbonyldiimidazole (11.7 g, 65.6 mmol, Eq: 1.2) The reaction was gradually warmed to room temperature and stirred overnight. The reaction was concentrated and chromatographed (220 g Redisep, 5 to 15% dichloromethane/hexane) to give 13.84 g (80%) pale yellow oil.
Reaction SMILES: [C:1]1(=[O:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.II.[CH2:10](O)[CH2:11][OH:12]>C(OCC)(=O)C>[O:7]1[C:1]2([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[O:12][CH2:11][CH2:10]1
Reactant: OCCO
Reactant: O=C1CCCCC1
Agent: II
Solvent: CCOC(C)=O
Product: C1CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.9 %

Procedure:
To a solution of cyclohexanone (10 g, 0.102 mol) in ethylene glycol (50 mL) was added iodine (3.88 g, 15.3 mmol) and the resulting mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate and extracted with saturated aqueous sodium thiosulfate. The organic phase was dried and concentrated to give a crude product, which was purified via silica gel chromatography eluting with ethyl acetate/petroleum ether (1:8) to give 1,4-dioxaspiro[4.5]decane (6.8 g, 46.9% yield) as light oil. 1H-NMR (CDCl3) δ 3.93(s, 4H), 1.58-1.59 (d, 8H), 1.39-1.41(m, 2H).
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12]([C:13]=2[CH:15]=O)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[CH3:17][N:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[NH2:19]>Cl.C(O)C>[CH3:17][N:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[N:19]=[CH:15][C:13]1[C:14]2[C:5]([CH:6]=[C:7]3[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]3)=[CH:4][CH:3]=[CH:2][CH:1]=2
Reactant: O=Cc1c2ccccc2cc2ccccc12
Reactant: CN(N)c1ccccc1
Agent: Cl
Solvent: CCO
Product: CN(N=Cc1c2ccccc2cc2ccccc12)c1ccccc1

Procedure:
3.1 g of anthracene-9-aldehyde and 1.8 g of 1-methyl-1-phenylhydrazine were added to 50 ml of ethanol. To the mixture, two or three drops of 1 N hydrochloric acid were added. The mixture was heated and refluxed for about one hour. The reaction mixture was cooled and the crystals then separated, which were then collected on a suction funnel. The thus obtained crude anthracene-9-aldehyde 1-methyl-1-phenylhydrazone was recrystallized from ethyl acetate. The yield was 2.3 g (48.9%) of yellow needle-like crystals which melt at 162.0°-162.5° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1.C(O)C.[BH4-].[Na+].Cl>O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([CH:22]([C:23]([F:26])([F:25])[F:24])[OH:27])[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(-c2cc(C(=O)C(F)(F)F)[nH]c2-c2ccc(OC)cc2)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1ccc(-c2cc(C(O)C(F)(F)F)[nH]c2-c2ccc(OC)cc2)cc1
Reaction time: 0.5 h
Yield: 84.8 %

Procedure:
To a stirred mixture of 1.9 g (0.005 mole) of 1-[4,5-bis(4-methoxyphenyl)-1H-pyrrol-2-yl]-2,2,2-trifluoro-1-ethanone and 25 ml ethanol at 0° was added 0.4 g (0.01 mole) of sodium borohydride all at once. The mixture was stirred at 0° 0.5 hour, then at room temperature 1 hour. The mixture was chilled in an ice bath and 40 ml of 1N hydrochloric acid was added dropwise. The mixture was poured into water and extracted with methylene chloride. The organic layers were dried and concentrated. The crude solid was triturated with methylcyclohexane and collected to give 1.6 g of product, m.p. 84°-86°.
Reaction SMILES: C(O[CH:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=O)C.[N:18]1([S:24]([C:27]2[NH:28][C:29]3[C:34]([CH:35]=2)=[CH:33][CH:32]=[CH:31][CH:30]=3)(=[O:26])=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>>[C:12]1([CH:5]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:35]2[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[NH:28][C:27]=2[S:24]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)(=[O:25])=[O:26])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=S(=O)(c1cc2ccccc2[nH]1)N1CCCCC1
Reactant: CC(=O)OC(c1ccccc1)c1ccccc1
Product: O=S(=O)(c1[nH]c2ccccc2c1C(c1ccccc1)c1ccccc1)N1CCCCC1
Yield: 81.7 %

Procedure:
Substantially the same procedure as in Example 263 was repeated using benzhydryl acetate (0.78 g, 3.41 mmol) and 2-(piperidinosulfonyl)indole (0.95 g, 3.59 mmol) to give 1.2 g (yield: 75%) of the title compound.