反应详情

A round-bottomed flask was charged with N-((4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (rac-4l, 0.233 g, 0.589 mmol), DCM (8 mL), N,N-diisopropylethylamine (0.133 mL, 0.766 mmol), 5-chloro-3-methylpicolinic acid (intermediate 6) 0.131 g, 0.766 mmol) and finally with 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate; 0.347 mL, 0.589 mmol). The reaction mixture was stirred at room temperature for 15 min. The Reaction mixture was poured into aqueous saturated NaHCO3 (50 mL) and then extracted with EtOAc (2×50 mL). The combined extracts were washed with brine, dried over Na2SO4 and loaded onto silica gel. Purification by silica gel chromatography (gradient 0 to 30% EtOAc/hexane) gave the title compound (50 mg). MS m/z=549.1 [M+H]+. Calculated for C26H21ClF4N4O3: 548.9

1. extractionextracted with EtOAc (2×50 mL)
2. washThe combined extracts were washed with brine
3. dry with materialdried over Na2SO4
4. customPurification by silica gel chromatography (gradient 0 to 30% EtOAc/hexane)