反应详情

8-bromo-7-fluoro-2-methoxy-[1,5]naphthyridine (prepared as in WO 2004/058144; 7 g, 27.2 mmol), trans-phenylvinyl boronic acid (4.23 g, 1.05 eq) and K2CO3 (4.9 g) were introduced in a two-necked flask. The atmosphere was flushed with nitrogen and dioxane (40 ml) and water (10 ml) were added. The mixture was stirred at rt for 5 min and Pd(PPh3)4 (1.56 g, 5 mol %) was added. The mixture was heated at reflux overnight. After cooling, the solvent was evaporated in vacuo and the residue was extracted with EA (2×150 ml). The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was chromatographed (Hept-EA 2-1) to afford the title compound (7.2 g, 94% yield) as a white solid.

1. customThe atmosphere was flushed with nitrogen and dioxane (40 ml) and water (10 ml)
2. additionwere added
3. additionPd(PPh3)4 (1.56 g, 5 mol %) was added
4. temperatureThe mixture was heated
5. temperatureat reflux overnight
6. temperatureAfter cooling
7. customthe solvent was evaporated in vacuo
8. extractionthe residue was extracted with EA (2×150 ml)
9. washThe combined extracts were washed with brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated to dryness
13. customThe residue was chromatographed (Hept-EA 2-1)