反应详情

Intermediate 60 (0.253 g, 0.83 mmol), EDC (0.223 g, 1.17 mmol) and HOBT (0.135 g, 1.0 mmol) in DMF (5 ml) was stirred at 20° C. for 30 minutes. t-Butyl carbazate (0.110 g, 0.83 mmol) was added and stirring continued for 18 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in DMF (5 ml) additional EDC (0.159 g0) and HOBT (0.112 g) added. After 30 minutes t-butyl carbazate (0.019 g) was added and stirring continued for 18 hours. The reaction was concentrated in vacuo and the residue partitioned between DCM and water. The organic phase was washed with aqueous sodium hydrogen carbonate then evaporated in vacuo. The material was applied to a SPE cartridge (silica, 10 g) and eluted with cyclohexane:ethyl acetate (1:1 followed by 2:1) to afford Intermediate 62 as a white solid (0.19 g). LCMS showed MH+=419; TRET=2.35 min.

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionthe residue dissolved in DMF (5 ml) additional EDC (0.159 g0)
3. additionHOBT (0.112 g) added
4. additionAfter 30 minutes t-butyl carbazate (0.019 g) was added
5. stirringstirring
6. waitcontinued for 18 hours
7. concentrationThe reaction was concentrated in vacuo
8. customthe residue partitioned between DCM and water
9. washThe organic phase was washed with aqueous sodium hydrogen carbonate
10. customthen evaporated in vacuo
11. washeluted with cyclohexane:ethyl acetate (1:1 followed by 2:1)