反应详情

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with [4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricy-clo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate 273a (161 g, 0.30 mmol), isoxazol-3-amine (25 mg, 0.30 mmol), cesium carbonate (196 mg, 0.60 mmol), and 1,4-dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, tris(dibenzylideneacetone)dipalladium(0) (14.0 mg, 0.015 mmol) and xantphos (17 mg, 0.030 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×10 mL). The combined organic filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 30/1) to afford 286a (96 mg, 59%) as yellow solid. MS-ESI: [M+H]+ 542.8.

1. customA 25-mL round-bottomed flask equipped with a reflux condenser
2. customAfter bubbling nitrogen through the suspension for 10 minutes
3. customflush
4. temperatureheated
5. temperatureat reflux for 5 h
6. filtrationfiltered
7. washThe solid was washed with dichloromethane (2×10 mL)
8. concentrationThe combined organic filtrate was concentrated under reduced pressure
9. customThe residue was purified by silica-gel column chromatography
10. washeluting with dichloromethane/methanol (80/1 to 30/1)