反应详情

To a stirring solution of N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide (0.52 g, 0.98 mmol), dichlorobis(triphenylphosphine)palladium(II) (34 mg, 0.05. mmol), and lithium chloride (0.15 g, 3.56 mmol) in 1,4-dioxane (5 mL) was added 4-(tributylstannyl)pyridine (1.16 g, 3.14 mmol) and dioxane (5 mL). The reaction mixture was heated to reflux, stirred overnight, and then filtered through diatomaceous earth. The filtrate was partitioned between 3:1 chloroform:isopropanol and saturated aqueous sodium bicarbonate, and the layers separated. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified by chromatography over silica gel, eluting with a step gradient of 10-25% 2 M ammonia/methanol solution in dichloromethane. The chromatography product was recrystallized from methanol and ethyl acetate to give 47 mg (10%) of a white solid.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux
3. filtrationfiltered through diatomaceous earth
4. customThe filtrate was partitioned between 3:1 chloroform
5. customisopropanol and saturated aqueous sodium bicarbonate, and the layers separated
6. dry with materialThe organic phase was dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by chromatography over silica gel
10. washeluting with a step gradient of 10-25% 2 M ammonia/methanol solution in dichloromethane
11. customThe chromatography product was recrystallized from methanol and ethyl acetate