反应详情

温度

55 °C

A 5 N aqueous sodium hydroxide solution (0.3 mL) was added to a solution of ethyl 5-[2,5-difluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate (157 mg) in ethanol (3 mL), and the mixture was stirred at 55° C. for two hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The residue was partitioned by adding chloroform, 5 N hydrochloric acid and a saturated aqueous ammonium chloride solution. The organic layer was dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure to give 5-[2,5-difluoro-4-(2-methoxy-4,6-dimethyl-pyridin-3-yl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid (155 mg) as a crude purified product. The carboxylic acid (155 mg) was dissolved in DMF (1 mL) and THF (3 mL). CDI (108 mg) was then added, and the mixture was stirred at room temperature for about 1.5 hours. A 28% aqueous ammonia solution (0.35 mL) was added to the reaction mixture, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and brine. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was solidified by adding n-heptane/MTBE (119) to give the title compound (82 mg). The title compound was used for the next reaction without further purification.

1. temperatureThe reaction mixture was cooled to room temperature
2. concentrationconcentrated under reduced pressure
3. customThe residue was partitioned
4. additionby adding chloroform, 5 N hydrochloric acid
5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
6. customThe desiccant was removed by filtration
7. concentrationthe filtrate was concentrated under reduced pressure