反应详情

To a solution of (R)—N-(1-(3-(1-amino-2-methyl-1-oxopropan-2-yloxy)-4-fluorophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 274, 30 mg, 0.046 mmol) in DMF (1 mL) at room temperature was added thionyl chloride (3 drops). The reaction mixture was stirred for 40 min and diluted with H2O and EtOAc. The organic layer was washed with H2O, saturated NaHCO3, H2O and saturated NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give pure (R)—N-(1-(3-(2-cyanopropan-2-yloxy)-4-fluorophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 275, 16 mg, yield: 55%). LCMS: RT=2.21 min [M+H] 633.3 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm).

1. washThe organic layer was washed with H2O, saturated NaHCO3, H2O and saturated NaCl
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe resulting residue was purified by flash chromatography (silica gel, hexanes/EtOAc)