反应详情

温度

40 °C

HOBt (0.024 g, 0.175 mmol) and EDCl.HCl (0.034 g, 0.175 mmol) were added to a solution of lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)-4-fluorophenyl)acetate (A53) (0.089 g, 0.146 mmol) and Et3N (0.082 mL, 0.585 mmol) in DMF (5 mL) and the resulting mixture stirred at 40° C. overnight. Saturated aqueous NaHCO3 (25 mL) and DCM (25 mL) were added then the layers separated and the aqueous phase extracted with CHCl3 (3×25 mL). The organics were combined then the volatiles were evaporated in vacuo. The residue was adsorbed onto silica gel and purified using column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to yield a clear oil. The oil was triturated with water and the resulting precipitate collected by filtration to give the title compound A54 as a white solid (0.065 g, 74%); 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J=1.0 Hz, 1H), 7.46 (d, J=8.2 Hz, 3H), 7.18-7.09 (m, 3H), 6.95-6.84 (m, 2H), 5.24 (d, J=21.9 Hz, 2H), 4.18 (s, 2H), 3.60 (s, 2H), 3.02 (s, 4H), 2.74 (t, J=10.2 Hz, 2H), 2.58 (m, 1H), 1.76 (d, J=11.7 Hz, 2H), 1.64-1.51 (m, 2H), 1.42 (s, 9H). LCMS-A: rt 6.477 min; m/z 602 [M+H]+.

1. customthe layers separated
2. extractionthe aqueous phase extracted with CHCl3 (3×25 mL)
3. customthe volatiles were evaporated in vacuo
4. custompurified
5. customcolumn chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)
6. customto yield a clear oil
7. customThe oil was triturated with water
8. filtrationthe resulting precipitate collected by filtration