Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[CH:17]=[C:16]2[C:18](=[O:23])[C:19]([F:22])([F:21])[CH2:20][C:15]2=[N:14]1.[CH3:24][Mg]Br.C([O-])(O)=O.[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[CH:17]=[C:16]2[C:18]([CH3:24])([OH:23])[C:19]([F:22])([F:21])[CH2:20][C:15]2=[N:14]1
Reactant: O=C1c2cn(-c3c(Cl)cc(C(F)(F)F)cc3Cl)nc2CC1(F)F
Reactant: C[Mg]Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1(O)c2cn(-c3c(Cl)cc(C(F)(F)F)cc3Cl)nc2CC1(F)F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 98 %

Procedure:
To a solution of (91) (3.6 mg, 9.7 mmol) in 300 mL THF was added methyl magnesium bromide (50 mL, 3.0 M) at 0° C. The solution was then stirred at room temperature for 30 min. The mixture was poured into 5 mL of saturated NaHCO3 solution and extracted with dichlormethane (5 mL×3). The organic layers were combined, washed with brine, and dried with anhydrous sodium sulfate. The mixture was then chromatographed on a silica gel TLC plate using hexane/ethyl acetate (3:1) to give (93): yield 98%; 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 2H), 7.47 (s, 1H), 3.65-3.31 (m, 2H), 2.46 (br s, 1H), 1.67 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:6][N:5]([C:7]2[CH:17]=[CH:16][C:10]([C:11]([O:13]CC)=O)=[CH:9][CH:8]=2)[C:4](=[O:18])[CH2:3]1.[CH:20]1([C:23]2[CH:24]=[C:25]([CH3:35])[C:26]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[N:27][CH:28]=2)[CH2:22][CH2:21]1>>[CH:20]1([C:23]2[CH:24]=[C:25]([CH3:35])[C:26]([N:29]3[CH2:30][CH2:31][N:32]([C:11]([C:10]4[CH:9]=[CH:8][C:7]([N:5]5[CH2:6][C:2]([CH3:1])([CH3:19])[CH2:3][C:4]5=[O:18])=[CH:17][CH:16]=4)=[O:13])[CH2:33][CH2:34]3)=[N:27][CH:28]=2)[CH2:22][CH2:21]1
Reactant: CCOC(=O)c1ccc(N2CC(C)(C)CC2=O)cc1
Reactant: Cc1cc(C2CC2)cnc1N1CCNCC1
Product: Cc1cc(C2CC2)cnc1N1CCN(C(=O)c2ccc(N3CC(C)(C)CC3=O)cc2)CC1
Yield: 14.8 %

Procedure:
Using ethyl 4-(4,4-dimethyl-2-oxopyrrolidin-1-yl)benzoate (131 mg) described in Preparation Example 49 and 1-(5-cyclopropyl-3-methylpyridin-2-yl)piperazine (109 mg) described in Preparation Example 83 and by the reaction and treatment in the same manner as in Example 109, the title compound (32 mg) was obtained.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]1[C:10]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][NH:8][N:7]=1)[CH3:4].Cl[CH2:19][C:20]1[CH:21]=[CH:22][C:23]([O:40][CH3:41])=[C:24]([CH:39]=1)[O:25][CH2:26][C:27]1[N:28]=[C:29]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:30][C:31]=1[CH3:32].O>CN(C)C=O>[CH2:3]([O:5][C:6]1[C:10]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][N:8]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([O:40][CH3:41])=[C:24]([O:25][CH2:26][C:27]3[N:28]=[C:29]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[O:30][C:31]=3[CH3:32])[CH:39]=2)[N:7]=1)[CH3:4]
Reactant: COc1ccc(CCl)cc1OCc1nc(-c2ccccc2)oc1C
Reactant: CCOC(=O)CCc1c[nH]nc1OCC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1cn(Cc2ccc(OC)c(OCc3nc(-c4ccccc4)oc3C)c2)nc1OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.1 %

Procedure:
Sodium hydride (60%, oily, 60.0 mg) was added to a solution of ethyl 3-(3-ethoxy-1H-pyrazol-4-yl)propionate (318 mg) and 4-(5-chloromethyl-2-methoxyphenoxymethyl)-5-methyl-2-phenyloxazole (516 mg) in N,N-dimethylformamide (10 ml) at 0° C., and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain ethyl 3-[3-ethoxy-1-[4-methoxy-3-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionate (647 mg, yield: 83%) as colorless crystals from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio). This was recrystallized from ethyl acetate-hexane. Melting point: 109–110° C.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[F:35][C:36]1[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][C:37]=1[C:45]([CH3:51])([CH2:48][CH2:49][OH:50])[CH2:46]O.[K]>ClCCl.O>[F:35][C:36]1[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][C:37]=1[C:45]1([CH3:51])[CH2:48][CH2:49][O:50][CH2:46]1
Reactant: CC(CO)(CCO)c1cc([N+](=O)[O-])ccc1F
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: [K]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: O
Product: CC1(c2cc([N+](=O)[O-])ccc2F)CCOC1
Temperature: 25 °C

Procedure:
To a solution of triphenylphosphine (2 eq) in dichloromethane at 0° C. under nitrogen was added dropwise triflic anhydride (1 eq). After 15 minutes 2-(2-fluoro-5-nitrophenyl)-2-methylbutane-1,4-diol (1 eq) was added in dichloromethane followed by potassium carbonated (1 eq). The resulting mixture was allowed to warm to room temperature for 5 h. To the mixture was added water and extracted with dichloromethane. The organic layer was washed with brine and dried with sodium sulfate and concentrated. Crude product was purified using flash chromatography (85% Hex:15% EtoAc) on silica to afford 3-(2-fluoro-5-nitrophenyl)-tetrahydro-3-methylfuran.
Reaction SMILES: C(O)(C(F)(F)F)=O.[NH:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=3)[CH:24]=2)[N:19](C2CCCCO2)[N:18]=1>C(Cl)Cl>[NH:10]1[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:8]=[C:9]1[C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:33])[F:34])[CH:27]=3)[CH:24]=2)[NH:19][N:18]=1
Reactant: FC(F)(F)c1cccc(-c2ccc3c(c2)c(-c2nc4ccccc4[nH]2)nn3C2CCCCO2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: FC(F)(F)c1cccc(-c2ccc3[nH]nc(-c4nc5ccccc5[nH]4)c3c2)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 50 %

Procedure:
TFA (0.5 mL, 6.490 mmol) was added to a solution 3-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(3-(trifluoromethyl)phenyl)-1H-indazole (8 mg, 0.017 mmol) in CH2Cl2 (4 mL). The reaction mixture was stirred at room temperature for 24 h, and then the solvent was removed in vacuo. Purification by flash chromatography (6% CH3OH/CH2Cl2) afforded the title compound as an off-white solid in a 50% yield. ESI-MS [M+H]+: 379.2.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[C:11]([CH2:14][CH:15]=[CH2:16])=[C:10]([C:17]([F:20])([F:19])[F:18])[NH:9]2)=[CH:4][C:3]=1[Cl:21].[Cl:22]Cl>C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[C:11]([CH2:14][CH:15]=[CH2:16])([Cl:22])[C:10]([C:17]([F:18])([F:19])[F:20])=[N:9]2)=[CH:4][C:3]=1[Cl:21]
Reactant: ClCl
Reactant: C=CCc1c(C(F)(F)F)[nH]n(-c2ccc(Br)c(Cl)c2)c1=O
Solvent: ClC(Cl)(Cl)Cl
Product: C=CCC1(Cl)C(=O)N(c2ccc(Br)c(Cl)c2)N=C1C(F)(F)F
Temperature: 0 °C
Reaction time: 15 h

Procedure:
A mixture of 4.06 g of the product of Step A and 150 ml of carbon tetrachloride was cooled to 0° C. and 17.2 ml of chlorine in solution in carbon tetrachloride (1.55 mole per liter) were added. When the reaction was complete, the product was washed with a saturated solution of sodium bicarbonate, with water, dried, treated with active charcoal and stirred for 15 hours, filtered and concentrated to obtain 51 g of 1-(4-bromo-3-chlorophenyl)-3-trifluoromethyl-4-allyl-4-chloro-5-pyrazolone.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1.[O-:23][S:24]([O-:26])=[O:25].[Na+:27].[Na+].O>CCO>[Na+:27].[CH2:16]([O:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][S:24]([O-:26])(=[O:25])=[O:23])=[CH:10][CH:11]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: BrCCCCCCCc1ccc(OCc2ccccc2)cc1
Reactant: O=S([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=S(=O)([O-])CCCCCCCc1ccc(OCc2ccccc2)cc1
Temperature: 25 °C

Procedure:
A stirred mixture of 10.1 (0.9 g, 2.50 mmol) and anhydrous Na2SO3 (0.423 g, 3.36 mmol) in EtOH (20 mL)/H2O (10 ml) was heated under reflux (6 h) or microwaved using a CEM-discover system (ram time: 2 min, hold time: 5 min, temperature: 150° C., pressure: 250 psi, power: 250 W). The reaction mixture was cooled to room temperature and the solvent evaporated under reduced pressure. The residue obtained was scrupulously dried under high vacuum and the crude product (10.1, pale yellow solid) was used in the next step without further purification.