反应详情

温度

70 °C

To a solution of 0.6 g of D-N-Boc-phenylglycine in 12 mL of dimethylformamide is added 0.74 g or O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU). After stirring for 5 minutes, 0.837 mL of triethylamine and 0.86 g of 3-[3-amino-4-(trifluoromethoxy)phenyl]-1-[(2-chloropyridin-4-yl)methyl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage c) below are successively added. The reaction mixture is heated at 70° C. for 15 hours and then poured into 100 mL of water. The aqueous phase is extracted with three times 70 mL of ethyl acetate and the combined organic phases are washed with 50 mL of saturated sodium chloride solution, dried over magnesium sulphate, filtered and evaporated. The residue is purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and ethyl acetate (70/30 by volume) to give 220 mg of (2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide, the characteristics of which are as follows:

1. extractionThe aqueous phase is extracted with three times 70 mL of ethyl acetate
2. washthe combined organic phases are washed with 50 mL of saturated sodium chloride solution
3. dry with materialdried over magnesium sulphate
4. filtrationfiltered
5. customevaporated
6. customThe residue is purified by chromatography on a column of silica
7. washeluting with a mixture of dichloromethane and ethyl acetate (70/30 by volume)