反应详情

温度

100 °C

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 270f (100 mg, 0.65 mmol, 1.7 eq.), (4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl acetate 217a (200 mg, 0.38 mmol, 1.0 eq.), DMF (10 mL), and cesium carbonate (499 mg, 1.52 mmol, 4.0 eq.). After bubbling nitrogen through the resulting solution for 10 minutes, Xantphos (44 mg, 0.076 mmol, 0.20 eq.) and tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol, 0.10 eq.) were added. The reaction mixture was subjected to three cycles of vacuum/argon flush and heated at 100° C. for 16 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (50 mL) and water (10 mL). The aqueous layer was separated and extracted with ethyl acetate (3×20 mL). The combined organic layer was concentrated under reduced pressure. The residue was purified on silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 270g (90 mg, 41%). MS-ESI: [M+H]+ 598.3.

1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customAfter bubbling nitrogen through the resulting solution for 10 minutes
3. customflush
4. temperatureAfter this time the reaction was cooled to room temperature
5. filtrationfiltered
6. customThe filtrate was partitioned between ethyl acetate (50 mL) and water (10 mL)
7. customThe aqueous layer was separated
8. extractionextracted with ethyl acetate (3×20 mL)
9. concentrationThe combined organic layer was concentrated under reduced pressure
10. customThe residue was purified on silica-gel column chromatography
11. washeluting with 50:1 dichloromethane/methanol