Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[C:16]([NH:17][S:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:23][CH:22]=3)(=[O:20])=[O:19])=[CH:15][C:14]([Cl:31])=[CH:13][N:12]=2)[CH:10]=1)=[O:5])C.[OH-].[Na+].C1COCC1>C(O)(=O)C>[C:27]([C:24]1[CH:25]=[CH:26][C:21]([S:18]([NH:17][C:16]2[C:11]([N:9]3[CH:10]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=[N:8]3)=[N:12][CH:13]=[C:14]([Cl:31])[CH:15]=2)(=[O:19])=[O:20])=[CH:22][CH:23]=1)([CH3:30])([CH3:28])[CH3:29]
Reactant: CCOC(=O)c1cnn(-c2ncc(Cl)cc2NS(=O)(=O)c2ccc(C(C)(C)C)cc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2cc(Cl)cnc2-n2cc(C(=O)O)cn2)cc1
Temperature: 80 °C
Reaction time: 16 h

Procedure:
A 25 mL scintillation vial was charged with 1-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (synthesized according to general procedure D, 93 mg, 0.2 mmol), NaOH (2 mL, 1.0 M solution in water), and THF (3 mL). The vial was sealed and stirred at 80° C. for 16 hours. The reaction solution was subsequently neutralized to pH=5 with glacial acetic acid. The mixture was extracted with ethyl acetate (2×10 mL) and the combined organics were concentrated in vacuo. The resultant residue was purified via preparative HPLC to afford 1-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-1H-pyrazole-4-carboxylic acid as a white powder: MS (ES) M+H expected 435.1, found 435.0.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.S(Cl)([Cl:14])=O>C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([Cl:14])=[O:11]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)Cc1ccccc1Cl
Solvent: CCOC(C)=O
Product: O=C(Cl)Cc1ccccc1Cl

Procedure:
2-Chlorophenylacetic acid (51 mg, 0.3 mmol) was dissolved in ethyl acetate (1.5 mL), the solution was added with thionyl chloride (26 μL, 0.36 mmol), and the mixture was refluxed by heating for 4 hours. The solvent was evaporated under reduced pressure to give 2-chlorophenylacetyl chloride. By using this compound and 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (190 mg, 0.6 mmol) obtained in Example 1, (3), the title compound (10 mg, yield 11%) was obtained as pale yellow crystals in the same manner as that of Example 1, (4).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2.[Li]C(C)(C)C.CO[C:17]1[CH:18]=[C:19]([CH:22]=CC=1OC)[CH:20]=O.[CH2:27]1[CH2:31][O:30][CH2:29][CH2:28]1>>[S:1]1[C:5]([CH:29]([OH:30])[C:28]2[CH:27]=[CH:31][C:18]([CH3:17])=[C:19]([CH3:22])[CH:20]=2)=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2
Reactant: COc1ccc(C=O)cc1OC
Reactant: C1CCOC1
Reactant: c1ccc2sccc2c1
Agent: [Li]C(C)(C)C
Product: Cc1ccc(C(O)c2cc3ccccc3s2)cc1C

Procedure:
α-(2-benzo[b]thienyl)-3,4-dimethylbenzyl alcohol was prepared in the same manner as described in Example 40A. Reaction of benzo[b]-thiophene (7.5 mmoles, 1.0 g), t-BuLi (1.7 m, 97 mmoles, 5.7 ml) and 3,4-dimethoxybenzaldehyde (8.9 mmoles, 1.5 g) in THF (20 ml) yielded, after flash chromatography using 30% ethyl acetate/hexanes, 2.25 g (≈100%) of a white gummy solid.
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH:11]=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.[C-:27]#[N:28].[Na+]>C(O)C>[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22]([O:12][CH:11]([C:10]2[CH:13]=[CH:14][CH:15]=[C:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:9]=2)[C:27]#[N:28])(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: O=Cc1cccc(Oc2ccccc2)c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)OC(C#N)c2cccc(Oc3ccccc3)c2)cc1
Reaction time: 0.5 h
Yield: 50.3 %

Procedure:
A mixture of 3.96 g of m-phenoxybenzaldehyde and 3.97 g of p-toluenesulfonyl chloride was stirred under ice cooling, and 10 ml of an aqueous solution containing 1.47 g of sodium cyanide was added dropwise over 30 minutes. Then, 10 ml of ethanol was added, and the mixture was stirred for 30 minutes under ice cooling, and then at room temperature for 30 minutes. The mixture was extracted with 30 ml of methylene chloride three times. The extract was washed with 20 ml of water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Recrystallization of the residue from ethanol afforded 3.816 g of O-(p-toluenesulfonyl)-m-phenoxymandelonitrile. The mother liquor was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel; hexane and benzene) to afford 1.846 g of O-(p-toluenesulfonyl)-m-phenoxymandelonitrile. The total amount of the product was 5.662 g (yield 75%). The product was in the form of colorless crystals.
Reaction SMILES: [CH:1]1([S:4]([NH:7][CH:8]2[CH2:12][CH:11](C(O)=O)[CH:10]([CH3:16])[CH2:9]2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.C1C=CC(P([N:31]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C[C:35]([OH:38])(C)C>>[N:31]([CH:11]1[CH:10]([CH3:16])[CH2:9][CH:8]([NH:7][S:4]([CH:1]2[CH2:2][CH2:3]2)(=[O:5])=[O:6])[CH2:12]1)=[C:35]=[O:38]
Reactant: CC(C)(C)O
Reactant: CC1CC(NS(=O)(=O)C2CC2)CC1C(=O)O
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Product: CC1CC(NS(=O)(=O)C2CC2)CC1N=C=O
Temperature: 70 °C
Yield: 80 %

Procedure:
To a solution of 4-(cyclopropanesulfonamido)-2-methylcyclopentanecarboxylic acid (4.10 g, 16.58 mmol, prepared from Example #24 Step I using Y, K, and Z) and DPPA (3.58 mL, 16.58 mmol) in t-BuOH (55 mL) was added TEA (5.0 mL, 36.5 mmol). The reaction was heated to about 70° C. for about 2 h then cooled to ambient temperature and concd under reduced pressure to afford a crude residue. The crude material was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM to afford N-(3-isocyanato-4-methylcyclopentyl)cyclopropanesulfonamide (3.25 g, 80%) as a white solid: LC/MS (Table 1, Method n) Rt=0.49 min; MS m/z: 245 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1[F:12])[N:8]=[CH:7][C:6]([C:14]([OH:16])=O)=[C:5]2[OH:17].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][NH2:39])=[CH:34][CH:33]=1>CN(C)C=O.O.C(N(CC)CC)C>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][NH:39][C:14]([C:6]2[CH:7]=[N:8][C:9]3[C:4]([C:5]=2[OH:17])=[CH:3][C:2]([F:1])=[C:11]([F:12])[C:10]=3[F:13])=[O:16])=[CH:34][CH:33]=1
Reactant: NNc1ccc(Cl)cc1
Reactant: O=C(O)c1cnc2c(F)c(F)c(F)cc2c1O
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=C(NNc1ccc(Cl)cc1)c1cnc2c(F)c(F)c(F)cc2c1O
Reaction time: 72 h

Procedure:
To a solution of 1.0 g of 6,7,8-trifluoro-4-hydroxy-3-quinolinecarboxylic acid (J. Amer. Chem. Soc., 68, 1264 (1946)). (The sample used in this procedure was shown by Karl Fisher titration to be a hydrate containing 0.4 equivalents of water.) in 15 mL of a 99:1 (v/v) mixture of dimethylformamide and triethylamine is added 1.01 g of carbonyldiimidazole. The mixture is stirred for 3 days and then it is transferred to a volumetric flask and diluted with dimethylformamide to a total volume of 25 mL. To 1.22 mL of this solution is added 39 mg of 4-chlorophenyl-hydrazine hydrochloride. The mixture is stirred 18 h at 25° C. and then 15 mL of distilled water is added. The precipitate is collected by filtration and dried in a stream of air. This procedure gives the title compound as 45 mg of a solid.
Reaction SMILES: O=[C:2]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[O:17][C:4]2([CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]2)[CH2:3]1.[NH2:24][OH:25].O>CO.C(OCC)(=O)C>[OH:25]/[N:24]=[C:2]1\[CH2:3][C:4]2([O:17][C:18]3[C:23]\1=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]2
Reactant: NO
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)CC(=O)c1ccccc1O2
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC2(CC1)C/C(=N\O)c1ccccc1O2
Reaction time: 24 h
Yield: 98 %

Procedure:
tert-Butyl 4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (450 mg, 1.41 mmol) and hydroxylamine 50 wt % in water (940 μL of 50% w/v, 14 mmol) were combined in methanol (9.0 mL) and heated at reflux. After 24 hours, the reaction mixture was diluted with ethyl acetate and was washed with water. The organics were dried over MgSO4, filtered and evaporated to dryness to yield (E)-tert-butyl 4-(hydroxyimino)spiro[chroman-2,4′-piperidine]-1′-carboxylate (450 mg, 98%). ESI-MS m/z calc. 332.4, found 333.3 (M+1)+; Retention time: 1.68 minutes (3 min run).