反应详情

To a mixture of 3-(3,5-dichlorophenyl)-1-[4-(methoxycarbonyl)benzyl]-1H-pyrazole-5-carboxylic acid (20 mg, 0.049 mmol), and PyBOP (36 mg, 0.069 mmol) in 1 mL of N,N-dimethylformamide was added N,N-diisopropylethylamine (15 μL, 0.088 mmol). After stirring at ambient temperature for 10 min, 2-aminothiophenol (7 μL, 0.059 mmol) was added, and stirring continued for 1 h. The resultant mixture was added drop-wise to 10 mL of glacial acetic acid containing dithiothreitol (15 mg, 0.097 mmol), and the mixture heated at 110° C. for 1 h. The acetic acid was removed in vacuo, the residue suspended in ethyl acetate and the organic layer washed successively with two portions of aqueous saturated sodium bicarbonate solution and one portion of brine. The organic layer was dried over magnesium sulfate, concentrated in vacuo, and the residue suspended in 2 mL of dioxane and 1 mL of water. Lithium hydroxide monohydrate (42 mg, 1.02 mmol) was added and the mixture heated at 50° C. for 2 h. The mixture was diluted with ethyl acetate and water and acidified with 1N hydrochloric acid solution. The organic layer was washed with one portion of brine, dried over magnesium sulfate, and concentrated in vacuo to provide the title compound which was used without purification. HPLC/MS: m/z=479.91 (M+1).

1. stirringstirring
2. waitcontinued for 1 h
3. temperaturethe mixture heated at 110° C. for 1 h
4. customThe acetic acid was removed in vacuo
5. washthe organic layer washed successively with two portions of aqueous saturated sodium bicarbonate solution and one portion of brine
6. dry with materialThe organic layer was dried over magnesium sulfate
7. concentrationconcentrated in vacuo
8. temperaturethe mixture heated at 50° C. for 2 h
9. washThe organic layer was washed with one portion of brine
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated in vacuo