Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C:9]1([CH3:27])[O:13][C:12]2[CH:14]=[CH:15][C:16]([F:26])=[C:17]([NH:18]C(=O)OC(C)(C)C)[C:11]=2[O:10]1.C(OCC)C.C(=O)(O)[O-].[Na+]>O>[NH2:18][C:17]1[C:11]2[O:10][C:9]([CH3:8])([CH3:27])[O:13][C:12]=2[CH:14]=[CH:15][C:16]=1[F:26]
Reactant: CC(C)(C)OC(=O)Nc1c(F)ccc2c1OC(C)(C)O2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: CCOCC
Product: CC1(C)Oc2ccc(F)c(N)c2O1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 65.2 %

Procedure:
In a flask was placed 50 mL of trifluoroacetic acid which was cooled to 0° C. To this cooled trifluoroacetic acid was added 11.5 g (0.041 mole) of t-butyl N-(2,2-dimethyl-5-fluoro-1,3-benzodioxol-4-yl)carbamate. This mixture was allowed to warm to ambient temperature at which it was stirred for 90 minutes. Diethyl ether and water were added to the mixture which was made basic with sodium bicarbonate. The organic phase was separated from the aqueous phase, and the former was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was passed through a column of silica gel, eluting with methylene chloride/heptane (1:1). Product-containing fractions were combined and the solvent evaporated under reduced pressure, yielding 4.9 g of 4-amino-2,2-dimethyl-5-fluoro-1,3-benzodioxole as the residue. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [C:1](Cl)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[CH3:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][N:12]=[C:11]2[NH2:17]>N1C=CC=CC=1>[CH3:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][N:12]=[C:11]2[NH:17][C:1](=[O:5])[CH:2]=[CH:3][CH3:4]
Reactant: Cc1ccc2[nH]nc(N)c2c1
Reactant: C/C=C/C(=O)Cl
Solvent: c1ccncc1
Product: CC=CC(=O)Nc1n[nH]c2ccc(C)cc12
Reaction time: 12 h

Procedure:
0.33 cm3 of crotonyl chloride is added to 560 mg of 5-methyl-1H-indazole-3-amine, prepared as described in patent EP 909 720, in 30 cm3 of pyridine. The medium is allowed to return to about 19° C. over 12 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50° C.) and the residue is taken up in 25 cm3 of tetrahydrofuran, 25 cm3 of ethyl acetate and 25 cm3 of distilled water. The organic phase is washed with 2×25 cm3 of distilled water. The resulting solution is dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under reduced pressure (2 kPa; 50° C.). The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume) and collecting 20 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). After drying (90 Pa; 45° C.), 50 mg of N-(5-methyl-1H-indazol-3-yl)-2-butenamide (E form) are obtained in the form of a white solid melting at about 218° C.
Reaction SMILES: B(Cl)(Cl)Cl.C([O:12][C:13]1[CH:18]=[C:17]([O:19]CC2C=CC=CC=2)[C:16]([Br:27])=[CH:15][C:14]=1[C:28]1[C:32]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[C:31]([CH3:41])[O:30][N:29]=1)C1C=CC=CC=1>ClCCl>[Br:27][C:16]1[CH:15]=[C:14]([C:28]2[C:32]([C:33]3[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=3)=[C:31]([CH3:41])[O:30][N:29]=2)[C:13]([OH:12])=[CH:18][C:17]=1[OH:19]
Reactant: COc1ccc(-c2c(-c3cc(Br)c(OCc4ccccc4)cc3OCc3ccccc3)noc2C)cc1
Agent: ClB(Cl)Cl
Solvent: ClCCl
Product: COc1ccc(-c2c(-c3cc(Br)c(O)cc3O)noc2C)cc1
Reaction time: 1 h
Yield: 43 %

Procedure:
Boron trichloride solution (1M in dichloromethane, 1 ml, μmol) was added to a solution of 3-(2,4-Bis-benzyloxy-5-bromo-phenyl)-4-(4-methoxy-phenyl)-5-methyl-isoxazole (38 mg, 0.068 mmol) in dichloromethane (1 ml), and stirring was continued for 1 h. The reaction mixture was partitioned between water (20 ml) and dichloromethane (2×20 ml) and the combined organic phases were dried over anhydrous magnesium sulphate and concentrated in vacuo to leave a brown oil. The crude product was purified by column chromatography, silica (10 g), eluting with hexane, followed by hexane/diethyl ether (3:1 then 1:1), to give 4-Bromo-6-[4-(4-methoxy-phenyl)-5-methyl-isoxazol-3-yl]-benzene-1,3-diol as a colourless oil (11 mg, 43%).
Reaction SMILES: [CH2:1]([C@@:4]1([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:20]([F:22])[F:21])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[OH2:30]>C1COCC1.C(Cl)Cl>[F:21][CH:20]([F:22])[O:19][C:16]1[CH:17]=[CH:18][C:13]([C@@H:11]([N:7]2[CH2:6][CH2:5][C@@:4]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)([CH2:1][CH2:2][CH2:3][OH:30])[O:9][C:8]2=[O:10])[CH3:12])=[CH:14][CH:15]=1
Reactant: O
Reactant: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(OC(F)F)cc2)C(=O)O1
Solvent: ClCCl
Solvent: C1CCOC1
Product: C[C@@H](c1ccc(OC(F)F)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O
Temperature: -9 °C
Reaction time: 21 h
Yield: 80 %

Procedure:
A solution of (R)-6-allyl-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (0.2780 g, 0.686 mmol, 1.0 equiv) in THF (20 mL) was degassed and then cooled with an ice-salt bath (−9° C.). To this solution was added a solution of 1.0 M BH3.THF complex in THF (1.5 mL, 1.5 mmol, 2.2 equiv). The resulting mixture was allowed to slowly warm to rt while stirring overnight (21 h) and then quenched with H2O (3 mL) and NaBO3.H2O (0.680 g, 6.8 mmol, 10 equiv). The mixture was vigorously stirred at rt overnight and then diluted with CH2Cl2, and dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to give 0.2337 g (80%) of (R)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one. LC-MS Method 1 tR=1.59 min, m/z 446 (MNa+), 380, 210, 171; 1H NMR (400 MHz, CD3OD) δ 7.27-7.23 (m, 2H), 7.04 (t, J=8.8 Hz, 2H), 6.94 (d, J=8.5 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 6.67 (t, J=74.1 Hz, 1H), 5.48 (q, J=7.1 Hz, 1H), 3.43-3.39 (m, 2H), 3.07-3.02 (m, 1H), 2.42-2.37 (m, 1H), 2.26-2.10 (m, 2H), 1.91-1.85 (m, 2H), 1.58-1.50 (m, 1H), 1.46 (d, J=7.0 Hz, 3H), 1.29-1.20 (m, 1H); 19F NMR (376 MHz, CD3OD) δ −83.95 (d, J=73.8 Hz), −117.51 (m).
Reaction SMILES: [CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[N:19]=[CH:18][C:17]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].ClCCl.[CH3:50][C:51]([CH3:53])=O>C(O)(=O)C>[CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[N:19]=[CH:18][C:17]([CH:20]4[CH2:25][CH2:24][N:23]([CH:51]([CH3:53])[CH3:50])[CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: CC(C)=O
Reactant: CN(C)C(=O)c1cc2cnc(Nc3ccc(C4CCNCC4)cn3)nc2n1C1CCCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC(C)N1CCC(c2ccc(Nc3ncc4cc(C(=O)N(C)C)n(C5CCCC5)c4n3)nc2)CC1
Yield: 60 %

Procedure:
To a suspension of 7-cyclopentyl-2-(1′,2′,3′,4′,5′,6′-hexahydro-[3,4]bipyridinyl-6-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (100 mg, 0.23 mmol) in dichloromethane/acetone is added NaBH(OAc)3 (488 mg, 2.3 mmol) followed by 3 drops of glacial acetic acid. After reaction is completed and concentrated. Diluted with 100 mL of H2O and basified to pH12 with 50% NaOH solution dropwise (2 mL). Extracted with dichloromethane (3×100 mL) and concentrated to give 7-cyclopentyl-2-(1′-isopropyl-1′,2′,3′,4′,5′,6′-hexahydro-[3,4′]bipyridinyl-6-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (65 mg, 60%). MS (ESI) m/z 476.3 (M+H)+
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[CH3:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2].[NH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>CS(C)=O>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[C:11]=2[CH3:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2]
Reactant: C1CNCCN1
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(F)c(C)c21
Solvent: CS(C)=O
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCNCC3)c(C)c21
Reaction time: 18 h
Yield: 11.5 %

Procedure:
A mixture of 1-ethyl-6,7-difluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylic acid (350 mg), anhydrous piperazine (450 mg) in anhydrous DMSO (4 ml) was stirred at 50° to 72° C. for 18 hours. After the reacting mixture was concentrated under reduced pressure, the resulting residue was purified by silica gel column chromatography eluting chloroform-methanol-concentrated aqueous ammonia (20:6:1) to give the title compound (50 mg) as pale yellow flakes, mp 153°-156° C.