反应详情

温度

68 °C

To a solution of (S)-tert-butyl 4-(1-amino-3-(4′-cyanobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (produced in step (ii), 35 g) in DMF (2.5 rel. vol.) at room temperature was added diisopropylethylamine (4 mol. eq.) and T3P in DMF (50% wt/wt in DMF, 3 mol. eq.) under nitrogen. The resulting mixture was heated to 68° C. for 2 h. The reaction mixture was cooled to room temperature and quenched by dropwise addition of water (3 rel. vol.). The reaction mixture was stirred for 30 min and 2-methyltetrahydrofuran (15 rel. vol.) was added. The organic layer was washed with water (2×5 rel. vol.) followed is by saturated aqueous sodium hydrogen carbonate solution. The separated organic layer was concentrated to 10 rel. vol. under reduced pressure and then heated to 55° C. after which n-heptane (5 rel. vol.) was slowly added over a period of 15 min. The mixture was stirred for 30 min at 55° C. and then filtered, washed with n-heptane (2 rel. vol.) and dried at 50° C. to afford the sub-titled compound (26.2 g).

1. temperatureThe reaction mixture was cooled to room temperature
2. customquenched by dropwise addition of water (3 rel. vol.)
3. addition2-methyltetrahydrofuran (15 rel. vol.) was added
4. washThe organic layer was washed with water (2×5 rel. vol.)
5. concentrationThe separated organic layer was concentrated to 10 rel
6. temperaturevol. under reduced pressure and then heated to 55° C. after which n-heptane (5 rel. vol.)
7. additionwas slowly added over a period of 15 min
8. stirringThe mixture was stirred for 30 min at 55° C.
9. filtrationfiltered
10. washwashed with n-heptane (2 rel. vol.)
11. customdried at 50° C.