反应详情

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (15 mL), 118a (455 mg, 1.95 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (0.40 g, 1.5 mmol), and cesium carbonate (1.22 g, 3.75 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, XantPhos (87 mg, 0.15 mmol) and tris(dibenzylideneacetone)dipalladium(0) (70 mg, 0.075 mmol) were added, and the reaction mixture was heated at reflux for 15 h. After this time the reaction was cooled to room temperature, partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated and extracted with ethyl acetate (50 mL×2). The organic layers were combined, washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with 50:1 DCM/MeOH to afford 118b as a yellow solid (320 mg, 50%). LCMS: (M+H)+ 309. 1H NMR (500 MHz, DMSO) δ 11.85 (s, 1H), 8.23 (s, 1H), 8.02 (d, J=2.5, 1H), 7.35 (d, J=2.5, 1H), 5.77 (d, J=2, 1H), 3.46 (s, 3H), 1.83 (m, 1H), 0.90 (m, 2H), 0.64 (m, 2H)

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
2. temperaturereflux condenser
3. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
4. temperaturethe reaction mixture was heated
5. temperatureat reflux for 15 h
6. custompartitioned between ethyl acetate (30 mL) and water (30 mL)
7. customThe aqueous layer was separated
8. extractionextracted with ethyl acetate (50 mL×2)
9. washwashed with brine (50 mL)
10. dry with materialdried over sodium sulfate
11. customThe drying agent was removed by filtration
12. concentrationthe filtrate was concentrated under reduced pressure
13. customThe residue was purified on flash column
14. washeluting with 50:1 DCM/MeOH