反应详情

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (15 mL), (R)-(6-aminopyridin-3-yl) (3-methylmorpholino)methanone 248a (332 mg, 1.5 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (480 mg, 1.8 mmol), and cesium carbonate (978 mg, 3.0 mmol). After bubbling nitrogen through the suspension for 3 minutes, Xantphos (87 mg, 0.15 mmol) and tris(dibenzylideneacetone)dipalladium(0) (69 mg, 0.075 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 2.5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×50 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (2:1 to 1:2) to afford 249a (430 mg, 70%) as a yellow solid. MS-ESI: [M+H]+ 407.3

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customAfter bubbling nitrogen through the suspension for 3 minutes
3. customflush
4. temperatureheated
5. temperatureat reflux for 2.5 h
6. filtrationfiltered
7. washThe solid was washed with dichloromethane (2×50 mL)
8. concentrationthe combined filtrate was concentrated under reduced pressure
9. customThe residue was purified by silica-gel column chromatography
10. washeluting with petroleum ether/ethyl acetate (2:1 to 1:2)