Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[CH3:17]O>>[F:1][C:2]1[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:17])=[O:5]
Reactant: CO
Reactant: O=C(O)c1ccc(O)cc1F
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(O)cc1F
Temperature: 80 °C
Reaction time: 20.5 h
Yield: 85 %

Procedure:
To a round bottom containing 2-fluoro-4-hydroxybenzoic acid (5.34 g, 34.19 mmol) (commercially available from Matrix Scientific and TCI America) was added a cold solution of MeOH (50 mL) and sulfuric acid (2.0 mL). The mixture was heated to 80° C. and monitored with TLC. After 20.5 hours, the solvent was removed, and the mixture was diluted with diethyl ether. The organic phase was washed carefully two times with saturated. aqueous NaHCO3, once with brine, and then dried over anhydrous sodium sulfate. After filtration, the organic solvent was removed in vacuo to yield T31.1 as a white solid (5.82, 85% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.79 (1H, s), 7.75 (1H, t, J=8.8 Hz), 6.69 (1H, dd, J=8.6, 2.3 Hz), 6.62 (1H, dd, J=13.1, 2.2 Hz), 3.78 (3H, s).
Reaction SMILES: [NH2:1][C:2]1[C:3]([O:17]C)=[CH:4][CH:5]=[C:6]2[C:10]=1[CH:9]([CH2:11][CH2:12][NH:13][C:14](=[O:16])[CH3:15])[CH2:8][CH2:7]2.B(Br)(Br)Br>ClCCl>[NH2:1][C:2]1[C:3]([OH:17])=[CH:4][CH:5]=[C:6]2[C:10]=1[CH:9]([CH2:11][CH2:12][NH:13][C:14](=[O:16])[CH3:15])[CH2:8][CH2:7]2
Reactant: COc1ccc2c(c1N)C(CCNC(C)=O)CC2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC(=O)NCCC1CCc2ccc(O)c(N)c21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 61.1 %

Procedure:
To a solution of N-[2-(7-amino-6-methoxyindan-1-yl) ethyl]acetamide (1.1 g, 4.4 mmol.) in dichloromethane (20 mL) was added dropwise gradually boron tribromide (2.1 mL, 22.1 mmol.). The mixture was stirred for 30 minutes at the same temperature. The reaction mixture was poured into ice-water, which was subjected to extraction with 10% methanol/chloroform. The extract solution was dried over anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The residue was purified by means of silica gel column chromatography (chloroform:methanol=10:1) to afford N-[2-(7-amino-6-hydroxyindan-1yl)ethyl]acetamide (yield 630 mg, 61%). A portion of the product was dissolved in ethanol, to which was added a saturated hydrochloric acid/ethanol solution. The solvent was distilled off under reduced pressure. The resulting crystalline precipitate was recrystallized from ethanol to afford the title compound.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([O:14][CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].C=O.[C:23](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(O)(=O)C>[Cl:2][C:3]1[CH:4]=[C:5]([O:14][CH:15]2[CH2:20][CH2:19][N:18]([CH3:23])[CH2:17][CH2:16]2)[C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9]
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: COC(=O)c1cc(Cl)cc(OC2CCNCC2)c1C
Agent: C=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: COC(=O)c1cc(Cl)cc(OC2CCN(C)CC2)c1C
Temperature: 25 °C
Reaction time: 18 h
Yield: 100 %

Procedure:
A solution of methyl 5-chloro-2-methyl-3-(piperidin-4-yloxy)benzoate, hydrochloride (140 mg, 0.437 mmol) and formaldehyde (195 μl, 2.62 mmol) in methanol (3580 μl) and acetic acid (597 μl) was added portion wise sodium triacetoxyborohydride (278 mg, 1.312 mmol). The reaction was stirred for 18 h at RT, at which time it was concentrated. The residue was dissolved in water, neutralized with saturated sodium bicarbonate solution, and extracted with EtOAc (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, concentrated, and dried under high vacuum to give methyl 5-chloro-2-methyl-3-((1-methylpiperidin-4-yl)oxy)benzoate (0.130 g, 0.437 mmol, 99% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.61-1.73 (m, 2 H) 1.84-1.94 (m, 2 H) 2.18 (s, 3 H) 2.21-2.27 (m, 2 H) 2.28 (s, 3 H) 3.83 (s, 3 H) 4.54 (dt, J=7.14, 3.63 Hz, 1 H) 7.29 (d, J=2.02 Hz, 1 H) 7.32 (d, J=2.02 Hz, 1 H). MS(ES) [M+H]+ 298.1.
Reaction SMILES: CO[C:3]([C:5]1[CH:10]=[N:9][C:8]([C:11]([O:13]C)=O)=[CH:7][N:6]=1)=[O:4].[NH2:15][C:16]([CH3:21])([CH2:19][OH:20])[CH2:17][OH:18]>C(O)C>[OH:18][CH2:17][C:16]([NH:15][C:11]([C:8]1[CH:7]=[N:6][C:5]([C:3]([NH:15][C:16]([CH3:21])([CH2:19][OH:20])[CH2:17][OH:18])=[O:4])=[CH:10][N:9]=1)=[O:13])([CH3:21])[CH2:19][OH:20]
Reactant: CC(N)(CO)CO
Reactant: COC(=O)c1cnc(C(=O)OC)cn1
Solvent: CCO
Product: CC(CO)(CO)NC(=O)c1cnc(C(=O)NC(C)(CO)CO)cn1
Yield: 23.4 %

Procedure:
A solution of 500 mg of 2,5-dimethoxycarbonylpyrazine and 525 mg of 2-amino-2-methyl-1,3-propanediol in 3 cm3 of ethanol is heated at a temperature in the region of the reflux temperature for 90 minutes. The reaction mixture is filtered while hot. The white solid is washed with 5 cm3 of boiling ethanol. 200 mg of N,N′-bis(1,3-dihydroxy-2-methyl-2-propyl)pyrazine-2,5-dicarboxamide are thus obtained in the form of a white solid melting at 208° C. [1H NMR spectrum (400 MHz, CDCl3, δ at ppm): 1.34 (s, 6H: 2×CH3); 3.55 and 3.66 (2 dd, J=11 and 5.5 Hz, 8H: 4×OCH2); 5.01 (t, J=5.5 Hz, 4H: 4×OH); 8.22 (s, 2H: ═CH at 3 and ═CH at 6); 9.20 (s, 2H: 2×CONH)].
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[Cl:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][C:18]=1[CH:19]([S:28][C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[F:27]>C(Cl)Cl.CCOCC>[Cl:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][C:18]=1[CH:19]([S:28]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)=[O:9])[C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[F:27]
Reactant: Fc1ccc(F)c(C(Sc2ccc(Cl)cc2)c2ccncc2Cl)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: CCOCC
Product: O=S(c1ccc(Cl)cc1)C(c1cc(F)ccc1F)c1ccncc1Cl
Reaction time: 3 h

Procedure:
After 3-chloroperbenzoic acid (33 mg, 0.20 mmol) was added to a solution of the 3-chloro-4-[(4-chlorophenylthio)-(2,5-difluorophenyl)methyl]pyridine (75 mg, 0.20 mmol), which had been obtained in Example 341, in methylene chloride (10 ml), the mixture was stirred for 3 hours under ice cooling. The reaction mixture was diluted with ether (80 ml). The solution was washed with water and brine, and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=3:1), whereby the title compound (48 mg, 60%) was obtained as a diastereomeric mixture (1:1).