反应详情

CDI (21.4 g) was added at one time to a solution of 5-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylic acid (38.7 g) in DMF (290 mL) at room temperature, and the mixture was stirred at room temperature for 95 minutes. 28% aqueous ammonia (95 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 35 minutes. 28% aqueous ammonia (95 mL) was added again to the reaction mixture, and the mixture was stirred at room temperature for 90 minutes. The reaction mixture was concentrated under reduced pressure. Chloroform (250 mL) and water (80 mL) were added to the resulting residue, and the organic layer was separated. The aqueous layer was re-extracted with chloroform (50 mL). The combined organic layers were sequentially washed with a saturated aqueous ammonium chloride solution (60 mL×3) and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was passed through a silica pad (NH-silica gel). The filtrate was concentrated under reduced pressure to give the title compound (37.2 g).

1. stirringthe mixture was stirred at room temperature for 35 minutes
2. stirringthe mixture was stirred at room temperature for 90 minutes
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. additionChloroform (250 mL) and water (80 mL) were added to the resulting residue
5. customthe organic layer was separated
6. extractionThe aqueous layer was re-extracted with chloroform (50 mL)
7. washThe combined organic layers were sequentially washed with a saturated aqueous ammonium chloride solution (60 mL×3) and brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure