反应详情

At 0° C., NaH (60% by weight suspension in mineral oil, 30 mg, 0.75 mmol) was added to a solution of 3-(3,5-difluorophenyl)-5-methyl-N-(1H-pyrazol-4-ylmethyl)-4,5-dihydro-1,2-oxazole-5-carboxamide (200 mg, 0.62 mmol) in DMF (10 ml), and the mixture was stirred for 15 min. The mixture was then warmed to RT, and bromoacetonitrile (225 mg, 1.87 mmol) was added. The mixture was stirred at RT for h and then at 60° C. for 4 h. After cooling to RT, sulfuric acid (0.5M, 10 ml) was added, and the mixture was extracted with EtOAc (3×20 ml). The combined organic phases were then dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel using the mobile phase heptane/EtOAc, giving N-{[1-(cyanomethyl)-1H-pyrazol-4-yl]methyl}-3-(3,5-difluorophenyl)-5-methyl-4,5-dihydro-1,2-oxazole-5-carboxamide (144 mg, 64%).

1. stirringThe mixture was stirred at RT for h
2. waitat 60° C. for 4 h
3. temperatureAfter cooling to RT
4. extractionthe mixture was extracted with EtOAc (3×20 ml)
5. dry with materialThe combined organic phases were then dried over Na2SO4
6. customthe solvent was removed under reduced pressure
7. customThe residue was chromatographed on silica gel using the mobile phase heptane/EtOAc