反应详情

温度

130 °C

A sealed tube was charged with 115e (156 mg, 0.35 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 114e (134 mg, 0.35 mmol), Pd2(dba)3 (64 mg, 0.070 mmol), PCy3 (40 mg, 0.14 mmol), cesium carbonate (228 mg, 0.70 mmol), water (1 drop), and dioxane (9 mL). After three cycles of vacuum/argon flush, the mixture was heated at 130° C. for 16 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol and further purified with reverse-phase prep-HPLC to afford 115 (31 mg, 13%). MS-ESI: [M+H]+ 661.3. 1H NMR (500 MHz, DMSO-d6) δ 9.97 (s, 1H), 8.56 (d, J=5.0 Hz, 1H), 8.25 (d, J=5.0 Hz, 1H), 8.19 (d, J=0.5 Hz, 1H), 7.95 (s, 1H), 7.68 (d, J=1.0 Hz, 1H), 7.48-7.44 (m, 3H), 6.58 (s, 1H), 4.76 (t, J=5.0 Hz, 1H), 4.58-4.54 (m, 3H), 4.49-4.46 (m, 1H), 4.43-4.36 (m, 2H), 4.30-4.05 (m, 3H), 3.94-3.87 (m, 2H), 3.42-3.37 (m, 1H), 3.24-3.19 (m, 1H), 3.00-2.96 (m, 1H), 2.66-2.57 (m, 3H), 2.47-2.43 (m, 3H), 2.28-2.26 (m, 1H), 2.12-2.09 (m, 1H), 1.79-1.68 (m, 4H), 1.00 (d, J=6.5 Hz, 3H).

1. customAfter three cycles of vacuum/argon flush
2. temperatureIt was then cooled to room temperature
3. filtrationfiltered
4. concentrationThe filtrate was concentrated under reduced pressure
5. customthe resulting residue was purified by silica-gel column chromatography
6. washeluting with 40:1 dichloromethane/methanol
7. customfurther purified with reverse-phase prep-HPLC