反应详情

Crude compound 9 and THF (6 L) were added to a 12 L round-bottom flask and stirred until the clear solution was obtained. A solution of ammonia in methanol (1.24 L; 7M) was added and stirred for 24 h at 28-35° C. The reaction mixture was concentrated to near dryness after with methanol was added and concentrated at 45-50° C. The separated solid was filtered and dried at 45-50° C. under vacuum to obtain crude compound 10 (601.7 g; Purity=≧95%; Yield=85.4%). Recrystallization of the crude in acetone/methanol (2:1) provided compound 10 in 74% yield with a purity of 98.5%. 1H NMR (DMSO-d6): δ (ppm) 9.78 (s, 1H), 8.72-8.73 (d, J=2.2 Hz, 1H), 8.65 (brs, 1H), 8.26 (s, 1H), 7.79-7.82 (d, J=8.5 Hz, 2H), 7.57-7.61 (m, 3H), 7.28-7.32 (t, J=8.3 Hz, 1H), 2.50-2.52 (m, 2H), 1.73-1.78 (m, 2H), and 0.96-0.98 (t, 3H). MS (ESI) [M+H+]+=490.1 and 492.1.

1. customwas obtained
2. stirringstirred for 24 h at 28-35° C
3. concentrationThe reaction mixture was concentrated
4. additionwas added
5. concentrationconcentrated at 45-50° C
6. filtrationThe separated solid was filtered
7. customdried at 45-50° C. under vacuum
8. customto obtain crude compound 10 (601.7 g; Purity=≧95%; Yield=85.4%)
9. customRecrystallization of the crude in acetone/methanol (2:1)