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), 126c (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. The reaction mixture was refluxed for 15 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated and extracted with ethyl acetate (2×50 mL). The combined organic layer was 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 silica-gel column eluting with 50:1 dichloromethane/methanol to afford 126d as a yellow solid (320 mg, 70%). MS: [M+H]+ 309. 1H NMR (500 MHz, DMSO-d6) δ 11.85 (s, 1H), 8.23 (s, 1H), 8.02 (d, J=2.5 Hz, 1H), 7.35 (d, J=2.5 Hz, 1H), 5.77 (d, J=2.0 Hz, 1H), 3.46 (s, 3H), 1.84-1.82 (m, 1H), 0.92-0.90 (m, 2H), 0.65-0.64 (m, 2H).

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
3. temperatureThe reaction mixture was refluxed for 15 h
4. filtrationfiltered
5. customThe filtrate was partitioned between ethyl acetate (30 mL) and water (30 mL)
6. customThe aqueous layer was separated
7. extractionextracted with ethyl acetate (2×50 mL)
8. washThe combined organic layer was washed with brine (50 mL)
9. dry with materialdried over sodium sulfate
10. customThe drying agent was removed by filtration
11. concentrationthe filtrate was concentrated under reduced pressure
12. customThe residue was purified on silica-gel column
13. washeluting with 50:1 dichloromethane/methanol