Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:5]=[C:6]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[H-].[Na+].[CH:32]1(Br)[CH2:36][CH2:35][CH2:34][CH2:33]1.[NH4+].[Cl-]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]([CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)[C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:5]=[C:6]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:18][CH:19]=2)[C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11]
Reactant: CCOC(=O)Cc1cc(Cl)c(OCC(F)(F)F)c(-c2ccc(C(F)(F)F)cc2)c1
Reactant: BrC1CCCC1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(c1cc(Cl)c(OCC(F)(F)F)c(-c2ccc(C(F)(F)F)cc2)c1)C1CCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 0 %

Procedure:
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.8 g, 1.8 mmol) was dissolved in anhydrous DMF (40 mL), NaH (60% wt. in paraffin oil, 0.052 g, 2.18 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and cyclopentyl bromide (0.298 g, 1.99 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×50 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-2-cyclopentylacetate (0.4 mg) as a thick liquid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:6]([CH2:7][N:8]=[N+:9]=[N-:10])=[CH:5][CH:4]=1.[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])#[N:14]>C1(C)C(C)=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:14][N:10]=[N:9]2)=[CH:11][CH:12]=1
Reactant: COc1ccc(CN=[N+]=[N-])cc1
Reactant: CCOC(=O)C#N
Solvent: Cc1ccccc1C
Product: CCOC(=O)c1nnnn1Cc1ccc(OC)cc1
Yield: 95.3 %

Procedure:
A mixture of crude 4-methoxybenzyl azide (45.3 g; prepared as described below) and ethyl cyanoformate (33 g) in xylene (300 ml) was heated at reflux for 48 hours. The mixture was evaporated at below 40° C. and under reduced pressure to leave a residue of ethyl 1-(4-methoxybenzyl)-1H-tetrazole-5-carboxylate (69.36 g), m.p. 52° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:11][CH:10]=[CH:9][CH:8]=2)([O-])=O>C(O)(C)C.[Pd]>[NH2:1][C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:11][CH:10]=[CH:9][CH:8]=2
Reactant: CC(C)(C)OC(=O)NNc1c([N+](=O)[O-])cnc2ccccc12
Agent: [Pd]
Solvent: CC(C)O
Product: CC(C)(C)OC(=O)NNc1c(N)cnc2ccccc12
Reaction time: 2 h
Yield: 96.7 %

Procedure:
A suspension of tert-butyl N′-(3-nitroquinolin-4-yl)hydrazinecarboxylate (2.50 g, 8.22 mmol) in 150 mL of isopropanol was treated with 1.0 g of 10% palladium on carbon and the mixture was shaken under an atmosphere of hydrogen (3.8×105 Pa) for 2 h. The reaction mixture was then filtered through a pad of CELITE filter agent and rinsed with isopropanol, and the filtrate was concentrated under reduced pressure to give tert-butyl N′-(3-aminoquinolin-4-yl)hydrazinecarboxylate (2.18 g) as a yellow solid.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][C:3]=1[CH:8]=[O:9].O[CH2:11][NH:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15].S(=O)(=O)(O)O>>[CH3:1][C:2]1[C:6]([CH2:11][NH:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])=[C:5]([CH3:7])[NH:4][C:3]=1[CH:8]=[O:9]
Reactant: O=C(NCO)C(F)(F)F
Reactant: Cc1cc(C)c(C=O)[nH]1
Agent: O=S(=O)(O)O
Product: Cc1[nH]c(C=O)c(C)c1CNC(=O)C(F)(F)F
Temperature: 25 °C

Procedure:
A mixture of 3,5-dimethylpyrrole-2-carboxaldehyde (2.6 g, 0.02 mol) and N-(hydroxymethyl)trifluoroacetamide (3 g, 0.02 mol) was added in portionwise to sulfuric acid (15 ml) keeping the temperature below 10° C. The mixture of reaction was allowed to warm at room temperature for 4 h. The reaction was poured into ice-water (100 ml), the precipitated solid was filtered and washed with water. The white solid (yield, 78%) was used without further purification. M.p. 200° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:21][S:22]([CH3:25])(=[O:24])=[O:23])=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)=[C:7]([C:17](O)=[O:18])[C:6]=2[CH:20]=1.C1C=CC2N(O)N=[N:32][C:30]=2C=1.CCN=C=NCCCN(C)C.CN>CN(C=O)C.CCN(CC)CC>[Br:1][C:2]1[C:3]([NH:21][S:22]([CH3:25])(=[O:24])=[O:23])=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)=[C:7]([C:17]([NH:32][CH3:30])=[O:18])[C:6]=2[CH:20]=1
Reactant: CS(=O)(=O)Nc1cc2oc(-c3ccc(F)cc3)c(C(=O)O)c2cc1Br
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: CN
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(NS(C)(=O)=O)c(Br)cc12
Reaction time: 2 h
Yield: 94.2 %

Procedure:
A solution of 5-bromo-2-(4-fluorophenyl)-6-(methylsulfonamido)benzofuran-3-carboxylic acid (33 g, 77 mmol), HOBT (15.6 g, 115.5 mmol) and EDCI (22.2 g, 115.5 mmol) in DMF (250 mL) was stirred at room temperature. After 2 hours, Et3N (50 mL) and CH3NH2 (HCl salt, 17.7 g, 231 mmol) was added to the mixture, and the mixture was stirred overnight. After the solvent was removed, H2O was added and the mixture was extracted with ethyl acetate. The combined organic layer was washed with H2O, brine and concentrated in vacuo. The resulting residue was washed with EtOAc to provide the product of 5-bromo-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide (32 g, yield: 94%). 1H-NMR (DMSO-d6, 400 MHz) δ 9.55 (br s, 1H), 8.46˜8.48 (m, 1H), 8.12˜8.17 (m, 2H), 7.96 (s, 1H), 7.87 (s, 1H), 7.45˜7.50 (m, 2H), 3.16 (s, 3H), 2.93 (d, J=8.4 Hz, 3H). MS (M+H)+: 441/443.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].[Cl:5][C:6]1[CH:11]=[C:10]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2F)(=[O:14])=[O:13])[CH:9]=[CH:8][C:7]=1[NH:22][C:23](=[O:31])[C@:24]([OH:30])([CH3:29])[C:25]([F:28])([F:27])[F:26].[Cl-].[NH4+]>CN1C(=O)CCC1>[Cl:5][C:6]1[CH:11]=[C:10]([S:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=2[NH:4][CH2:3][CH2:1][OH:2])(=[O:14])=[O:13])[CH:9]=[CH:8][C:7]=1[NH:22][C:23](=[O:31])[C@:24]([OH:30])([CH3:29])[C:25]([F:28])([F:27])[F:26]
Reactant: C[C@@](O)(C(=O)Nc1ccc(S(=O)(=O)c2ccccc2F)cc1Cl)C(F)(F)F
Reactant: NCCO
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN1CCCC1=O
Product: C[C@@](O)(C(=O)Nc1ccc(S(=O)(=O)c2ccccc2NCCO)cc1Cl)C(F)(F)F
Temperature: 120 °C

Procedure:
Ethanolamine (0.014 ml) was added to a solution of (R)-N-[2-chloro-4-(2-fluoro-phenylsulphonyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Method 63) (0.10 g) in NMP (1.5 ml) and the solution was heated at 120° C. for 18 hours then cooled. Saturated aqueous ammonium chloride solution (10 ml) was added and the mixture was extracted with ethyl acetate (2×20 ml). The organic extracts were combined, washed with brine and dried. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 0-50% ethyl acetate/hexane to give the title compound (0.074 g) as a solid. Mp 68-70° C.; NMR (CDCl3): 1.75 (s, 3H), 3.3 (q, 2H), 3.90 (m, 2H), 3.95 (brs, 1H), 6.50 (brt, 1H), 6.70 (d, 1H) 6.80 (m, 1H), 7.4 (m, 1H), 7.85 (m, 2H), 8.00 (d, 1H), 8.55 (d, 1H), 9.25 (brs, 1H); MS (ESP−): 465; EA: found: C, 46.6; H, 4.0; N, 5.8%; C18H18ClF3N2O5S requires: C, 46.31; H, 3.89; N, 6.00%.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:5]=2[N:6]=1.[Br:12]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:12][CH2:11][C:8]1[CH:9]=[CH:10][C:4]2[O:3][C:2]([CH3:1])=[N:6][C:5]=2[CH:7]=1
Reactant: Cc1ccc2oc(C)nc2c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: Cc1nc2cc(CBr)ccc2o1
Temperature: 25 °C

Procedure:
A mixture of commercially available 2,5-dimethylbenzo[d]oxazole (1.000 g; 6.79 mmol), N-bromosuccinimide (1.209 g; 6.79 mmol), and commercially available dibenzoyl peroxide (11 mg; 0.046 mmol) in anh. CCl4 (10 ml) was refluxed, under nitrogen, for 17 h. After cooling to rt, the reaction mixture was filtered, and the filtrate was concentrated to dryness under reduced pressure. Purification by FC (heptane/AcOEt=9/1) afforded 5-(bromomethyl)-2-methylbenzo[d]oxazole as a yellow solid. LC-MS (conditions E): tR=0.61 min.; [M+H]+: 226.12 g/mol.
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:26]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:25][CH2:24][CH2:23][CH2:22][C:21]([C:31](O)=[O:32])=[CH:20][C:19]=3[CH:34]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].CN(C=O)C.S(Cl)(Cl)=O.[CH2:44]([N:47]1[C:51]([CH2:52][S:53]([C:55]2[CH:61]=[CH:60][C:58]([NH2:59])=[CH:57][CH:56]=2)=[O:54])=[CH:50][N:49]=[CH:48]1)[CH2:45][CH3:46]>O1CCCC1.O.C(N(CC)CC)C>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:26]([CH2:27][CH:28]([CH3:29])[CH3:30])[CH2:25][CH2:24][CH2:23][CH2:22][C:21]([C:31]([NH:59][C:58]4[CH:60]=[CH:61][C:55]([S:53]([CH2:52][C:51]5[N:47]([CH2:44][CH2:45][CH3:46])[CH:48]=[N:49][CH:50]=5)=[O:54])=[CH:56][CH:57]=4)=[O:32])=[CH:20][C:19]=3[CH:34]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCn1cncc1CS(=O)c1ccc(N)cc1
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCCCN3CC(C)C)cc1
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)Cc4cncn4CCC)cc2)CCCCN3CC(C)C)cc1
Reaction time: 0.5 h

Procedure:
(−)-4-(((1-Propylimidazol-5-yl)methyl)sulfinyl)aniline di-p-toluoyl-D-tartarate monohydrate (932 mg) was dissolved in ethyl acetate (5 ml) and 1N hydrochloric acid (4.89 ml), followed by separation. To the aqueous layer was added an aqueous 25% potassium carbonate solution (4.89 ml), followed by extraction with 2-propanol-ethyl acetate (1:4) three times. The organic layers were combined and washed with saturated brine, dried with magnesium sulfate, and the solvent was distilled off under reduced pressure. To the resulting residue was added tetrahydrofuran, after which the solvent was distilled off again under reduced pressure to give (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline. Then, to a solution of 9-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-2,3,4,5-tetrahydro-1H-1-benzoazonin-6-carboxylic acid (500 mg) in tetrahydrofuran (10 ml) was added a drop of DMF and then thionyl chloride (0.102 ml) was added, and the mixture was stirred under nitrogen atmosphere for 30 minutes. The resulting solution was added dropwise to a solution of (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline and triethylamine (0.75 ml) in tetrahydrofuran (10 ml) at 0° C. under nitrogen atmosphere. The mixture was returned to room temperature and stirred for 3 hours, after which water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous acetic acid solution twice, with aqueous saturated sodium bicarbonate solution twice and with saturated brine once, after which the resultant was dried with magnesium sulfate. After distilling off the solvent under reduced pressure, the resultant was separated and purified with a basic silica gel column chromatography (hexane:ethyl acetate=1:4→ethyl acetate) to give (−)-9-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[[1-propylimidazol-5-yl]methyl]sulfinyl]phenyl]-2,3,4,5-tetrahydro-1H-1-benzoazonin-6-carboxamide (265 mg) (Compound 26) as a yellow amorphous material.