Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[CH:12][C:11]=2[C:15]([OH:17])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:18]([NH:20][CH2:21][CH3:22])[CH3:19]>>[CH2:18]([N:20]([CH2:21][CH3:22])[C:15]([C:11]1[CH:12]=[N:13][O:14][C:10]=1[C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1)=[O:17])[CH3:19]
Reactant: O=C(O)c1cnoc1-c1ccc([N+](=O)[O-])cc1
Reactant: CCNCC
Product: CCN(CC)C(=O)c1cnoc1-c1ccc([N+](=O)[O-])cc1

Procedure:
The title compound was prepared from 5-(4-nitrophenyl)isoxazole-4-carboxylic acid (11.7 mg, 0.050 mmol) and diethylamine (4.4 mg, 0.060 mmol) as described in synthetic method A and thereafter purified, first by preparative HPLC method A and then by method B, to give a solid (4.3 mg). MS (pos) m/z 290.2 (M+1).
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[C:14]([F:15])=[CH:13][C:7]([O:8][CH2:9][C:10]([OH:12])=[O:11])=[C:6]([OH:16])[CH:5]=1.[CH3:17][S:18]([C:21]1[CH:26]=[CH:25][C:24](F)=[C:23]([Cl:28])[CH:22]=1)(=[O:20])=[O:19]>CN(C=O)C>[Cl:28][C:23]1[CH:22]=[C:21]([S:18]([CH3:17])(=[O:20])=[O:19])[CH:26]=[CH:25][C:24]=1[O:16][C:6]1[CH:5]=[C:4]([F:3])[C:14]([F:15])=[CH:13][C:7]=1[O:8][CH2:9][C:10]([OH:12])=[O:11]
Reactant: O=C(O)COc1cc(F)c(F)cc1O
Reactant: CS(=O)(=O)c1ccc(F)c(Cl)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccc(Oc2cc(F)c(F)cc2OCC(=O)O)c(Cl)c1
Temperature: 85 °C

Procedure:
A mixture of sodium hydride (60% wt. disp. in oil, 0.275 g) and the product from step (iii) (0.7 g) in DMF (10 ml) was stirred at RT for 15 min. The product from example 7 step (ii) (0.715 g) was added and the mixture heated at 85° C. for 15 h. The mixture was partitioned between 2M sodium hydroxide solution and diethylether, the aqueous layer was acidified with 2M hydrochloric acid and extracted with ethylacetate. The ethylacetate layer was dried, evaporated under reduced pressure and the residue purified by RPHPLC. Yield 0.076 g.
Reaction SMILES: [SH2:1].[C:2]([CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:3].C(N(CC)CC)C.Cl>N1C=CC=CC=1>[CH2:9]([O:8][C:6]([CH2:5][CH2:4][C:2]([NH2:3])=[S:1])=[O:7])[CH3:10]
Reactant: CCOC(=O)CCC#N
Reactant: S
Agent: Cl
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: CCOC(=O)CCC(N)=S
Reaction time: 8 h

Procedure:
Hydrogen sulfide was introduced with stirring at room temperature into a solution of 31.8 g (0.25 mol) of ethyl 3-cyanopropionate and 34.6 ml (0.25 mol) of triethylamine in 75 ml of pyridine for 9 hours. After allowing to stand overnight, the reaction mixture is rendered acidic with 2N hydrochloric acid with cooling and extracted several times with ethyl acetate. The combined organic phase, which is dried over sodium sulfate, is carefully concentrated under reduced pressure. The oily residue remaining (35.0 g =87 % of theory) is composed of about 87 % of 3-(ethoxycarbonyl)thiopropionamide and 13 % of ethyl 3-cyanopropionate according to GC analysis.
Reaction SMILES: [H-].[Na+].Cl[C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[C:6]([Cl:13])[N:5]=1.[CH2:14]([OH:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O1CCCC1>[Cl:13][C:6]1[N:5]=[C:4]([O:21][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1Cl
Reactant: OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(Cl)nc1OCc1ccccc1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 82.6 %

Procedure:
2.0 g of sodium hydride was added to a mixture of 9.65 g of 2,6-dichloro-3-nitropyridine, 5.41 g of benzyl alcohol and 30 ml of tetrahydrofuran 0° C. The mixture was stirred at 0° C. for 1.5 hours, then at room temperature for 1.5 hours. The reaction solution was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 10.93 g of 6-chloro-2-benzyloxy-3-nitropyridine.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH2:7][CH2:6]2.B(Br)(Br)Br.CO.C([O-])(O)=O.[Na+]>ClCCl>[CH3:12][N:8]1[C:9]2[C:5](=[CH:4][C:3]([OH:2])=[CH:11][CH:10]=2)[CH2:6][CH2:7]1
Reactant: COc1ccc2c(c1)CCN2C
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CN1CCc2cc(O)ccc21
Reaction time: 0.5 h
Yield: 52.7 %

Procedure:
To a solution of 5-methoxy-1-methylindoline (131 mg, 0.802 mmol) in 4.0 mL of dry dichloromethane was added boron tribromide (0.38 mL, 4.0 mmol) under nitrogen at 0° C. After the reaction mixture was stirred at the same temperature for 30 min, methanol (1 mL) was added with additional stirring at room temperature for 5 min. After the reaction mixture was neutralized by saturated NaHCO3 aqueous solution, the solution was extracted with diethyl ether (20 mL) twice. The combined extracts were washed with brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=90/10 to 50/50) to obtain the title compound (63 mg, 53%).
Reaction SMILES: Cl[C:2]([O:4][CH3:5])=[O:3].[CH:6]1([OH:14])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.N1C=CC=CC=1.Cl.N1C=CC=CC=1>C1C=CC=CC=1>[C:2](=[O:3])([O:14][CH:6]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[O:4][CH3:5]
Reactant: COC(=O)Cl
Reactant: OC1CCCCCCC1
Agent: Cl
Solvent: c1ccncc1
Solvent: c1ccccc1
Product: COC(=O)OC1CCCCCCC1
Reaction time: 12 h

Procedure:
18.9 gm of methyl chloroformate were added drop-by-drop under agitation to a solution of 25.6 gm of cyclooctanol and 15.8 gm of absolute pyridine in 150 ml of dry benzene under external cooling at 0° to 5° C. After the methyl chloroformate had been added, agitation was continued for 12 hours at room temperature. Then, the benzene phase was drawn off from the precipitated pyridine hydrochloride, and washed with diluted hydrochloric acid, sodium hydroxide solution and water, and dried. After the solvent had been distilled off, the raw ester was distilled in vacuo by means of a Vigreux column. A colorless liquid was obtained which had a herbal, very natural and complex fragrance which is distinguished by a strong and long-clinging flowery jasmine scent.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](I)[S:9][CH:10]=1)=[O:5])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:31]([Si:33]([CH3:36])([CH3:35])[CH3:34])#[CH:32]>C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:34][Si:33]([CH3:36])([CH3:35])[C:31]#[C:32][C:8]1[S:9][CH:10]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[N:7]=1
Reactant: CCOC(=O)c1csc(I)n1
Reactant: C#C[Si](C)(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: CCOC(=O)c1csc(C#C[Si](C)(C)C)n1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
4-Ethoxycarbonyl-2-iodothiazole (6.39 g) was suspended in 60 ml of triethylamine, and 253 mg of palladium acetate and 592 mg of triphenylphosphine, and 6.37 ml of ethynyltrimethylsilane were added to the suspension under an argon atmosphere, followed by stirring at 80° C. for 2 hr. The reaction solution was concentrated under the reduced pressure, ethyl acetate and brine were added to the concentrate, and the mixture was adjusted to pH 3.0 by the addition of 1 N aqueous hydrochloric acid. The mixture was extracted twice with ethyl acetate and was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, was filtered, and was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1) to give 3.97 g of 2-(2-trimethylsilylethynyl)-4-ethoxycarbonylthiazole. This compound was dissolved in 30 ml of methanol, and the solution was cooled in ice. Potassium carbonate (220 mg) was added to the cooled solution, and the mixture was stirred at room temperature for 30 min. Brine was added to the reaction solution, and the mixture was extracted twice with ethyl acetate and was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, was filtered, and was concentrated under the reduced pressure to give 2.50 g of 2-ethynyl-4-methoxycarbonylthiazole.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=[C:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1.[S:21]1[C:25]([C:26]([C:28]2[N:29]([CH3:33])[CH:30]=[N:31][CH:32]=2)=[O:27])=[CH:24][C:23]2[CH:34]=[CH:35][CH:36]=[CH:37][C:22]1=2>>[S:21]1[C:25]([C:26]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=[C:5]3[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)([C:28]2[N:29]([CH3:33])[CH:30]=[N:31][CH:32]=2)[OH:27])=[CH:24][C:23]2[CH:34]=[CH:35][CH:36]=[CH:37][C:22]1=2
Reactant: COc1cc(-c2cccc(Cl)c2)c2cc(Br)ccc2n1
Reactant: Cn1cncc1C(=O)c1cc2ccccc2s1
Product: COc1cc(-c2cccc(Cl)c2)c2cc(C(O)(c3cc4ccccc4s3)c3cncn3C)ccc2n1
Yield: 61.8 %

Procedure:
Following the same procedure as described in example 1E, 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline (273 mg, 0.784 mmol) and benzo[b]thiophen-2-yl-(3-methyl-3H-imidazol-4-yl)-methanone (247 mg, 1.01 mmol) generated the title compound of 41A (248 mg, 62% yield).