反应详情

温度

0 °C

To a solution of triphosgene (1.38 g, 4.65 mmol) in Ethyl acetate (20 ml) at 0° C. a solution of 2-chloro-5-aminopyrimidine (1 g, 7.75 mmol)/DIPEA (8 ml, 4.65 mmol) in ethyl acetate (40 ml) was slowly added (20 minutes) and the reaction mixture was stirred for 15 minutes at the same temperature. Maintaining the reaction mixture at 0° C., vacuum was applied (10 minutes) for removing the excess of phosgene. A solution of DMAP (0.945 g, 7.75 mmol) in ethyl acetate/dichloromethane 1:1 (8 ml) was added and the reaction mixture was stirred for 5 minutes at the same temperature. A solution of methyl (R)-2-amino-2-methyl-butyrate hydrochloride (2.59 g, 15.5 mmol) in ethyl acetate (30 ml) was slowly added (15 minutes) at 0° C. and the reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with aqueous buffer (pH3) while the pH was allowed to reach ˜5-6 and two phases were separated. The organic layer was washed with aqueous buffer (pH3) (2×20 ml) and then brine (20 ml), dried (Na2SO4), filtered and evaporated affording the urea intermediate as orange foam.

1. custom(10 minutes)
2. customfor removing the excess of phosgene
3. stirringthe reaction mixture was stirred for 5 minutes at the same temperature
4. stirringthe reaction mixture was stirred for 30 minutes at the same temperature
5. customThe reaction was quenched with aqueous buffer (pH3) while the pH
6. customwere separated
7. washThe organic layer was washed with aqueous buffer (pH3) (2×20 ml)
8. dry with materialbrine (20 ml), dried (Na2SO4)
9. filtrationfiltered
10. customevaporated