反应详情

A microwave vial equipped with a magnetic stirrer was charged with 118b (200 mg, 0.52 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 (545 mg, 0.78 mmol), potassium carbonate (216 mg, 1.56 mmol), tris(dibenzylideneacetone) dipalladium(0) (48 mg, 0.052 mmol), tricyclohexylphosphine (146 mg, 0.52 mmol), water (0.2 mL), and dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, the sealed vial was irradiated under microwave at 110° C. for 1 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 118 as a white solid (50 mg, 15%). MS-ESI: [M+H]+ 646.3. 1H NMR (500 MHz, DMSO) δ 8.69 (d, J=2.0 Hz, 1H), 8.49 (d, J=5.0 Hz, 1H), 8.32-8.28 (m, 2H), 8.13 (s, 1H), 7.85-7.83 (m, 1H), 7.39-7.33 (m, 2H), 7.36 (s, 1H), 7.29 (s, 1H), 6.59 (s, 1H), 5.89 (s, 1H), 4.56 (t, J=6.5 Hz, 2H), 4.46 (t, J=6.5 Hz, 2H), 4.23-4.16 (m, 2H), 4.15-4.12 (m, 4H), 3.89-3.53 (m, 1H), 3.13-3.07 (m, 5H), 2.64-2.54 (m, 2H), 2.51-2.43 (m, 5H), 1.79-1.70 (m, 4H)

1. customA microwave vial equipped with a magnetic stirrer
2. customAfter bubbling nitrogen through the suspension for 10 minutes
3. customthe sealed vial was irradiated under microwave at 110° C. for 1 h
4. filtrationfiltered
5. concentrationThe filtrate was concentrated under reduced pressure
6. customthe residue was purified by reverse-phase prep-HPLC