反应详情

温度

0 °C

To a solution of (4S,6S)-4-(5-amino-2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.075 g, 0.232 mmol) and 5-(difluoromethyl)-3-methylpicolinic acid (0.048 g, 0.255 mmol) in DMF (2 mL) at 0° C. was added 1-propanephosphonic acid cyclic anhydride (0.177 ml, 0.278 mmol) and the resulting mixture was stirred at 0° C. for 2 h, the ice bath was removed and stirred at rt for 1 h. The reaction was diluted with EtOAc, washed with water, sat. NaHCO3, and chromatographed on silica gel using 0-4% MeOH/DCM to afford a white solid as N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluoro-5-methylphenyl)-5-(difluoromethyl)-3-methylpicolinamide (0.0145 g, 0.029 mmol, 12.69% yield). MS m/z=492.9 [M+H]+. Calculated for C21H19F7N4O2: 492.14.

1. customthe ice bath was removed
2. stirringstirred at rt for 1 h
3. additionThe reaction was diluted with EtOAc
4. washwashed with water, sat. NaHCO3
5. customchromatographed on silica gel using 0-4% MeOH/DCM