反应详情

To a stirred solution of indole 1 (Example 14, Step 2; 80 mg, 0.15 mmol) in THF (5 mL) under inert atmosphere were added Et3N (0.04 mL, 0.31 mmol) and triphosgene (18.3 mg, 0.06 mmol) at 0° C., stirred for 1 h, warmed to RT and stirred for 2 h. To this solution of crude isocyanate was passed ammonia gas at −78° C. for 10 min; warmed to 0° C. and stirred for 1 hr. The mixture was diluted with water and extracted with EtOAc (2×20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the crude. This was purified by triturating with Et2O (2×5 mL) and dried under reduced pressure to afford 2 (30 mg, 34%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.19 (s, 1H), 7.82 (s, 1H), 7.60 (t, J=7.2 Hz, 1H), 7.22-7.11 (m, 3H), 6.84 (t, J=7.2 Hz, 1H), 6.04-6.03 (m, 1H), 5.53 (br s, 2H), 4.33 (q, 2H), 4.21 (t, J=6.0 Hz, 2H), 3.43 (t, J=6.0 Hz, 2H), 1.84-1.78 (m, 1H), 1.32 (t, J=7.2 Hz, 3H), 0.92-0.91 (m, 2H), 0.87-0.85 (m, 2H); MS: m/z 560.6 (M+H+).

1. stirringstirred for 2 h
2. customat −78° C.
3. customfor 10 min
4. temperaturewarmed to 0° C.
5. stirringstirred for 1 hr
6. extractionextracted with EtOAc (2×20 mL)
7. dry with materialThe combined organic extracts were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto obtain the crude
11. customThis was purified
12. customby triturating with Et2O (2×5 mL)
13. customdried under reduced pressure