反应详情

温度

100 °C

tert-butyl 3-{7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-6-bromo-3-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-5-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate (0.550 g, 0.672 mmol), tributyl[1-(ethyloxy)ethenyl]stannane (681 μL, 2.02 mmol) and tetrakis(triphenylphosphine)palladium(0) (78 mg, 0.067 mmol) were placed in a 3-neck 25-mL round bottom flask equipped with a reflux condenser and rubber septa. Then, the flask was evacuated and back-filled with nitrogen three times before adding 1,4-dioxane (20 mL). The resulting solution was sparged with nitrogen for 15 minutes and then lowered into an oil bath that was heated at 100° C. and the resulting solution stirred overnight at the same temperature. Another portion of tetrakis(triphenylphosphine)palladium(0) (78 mg, 0.067 mmol) was added after 14 h, and the reaction allowed to progress for another 24 h, at which point, analysis showed consumption of the starting material and formation of the desired product. The reaction was cooled to ambient temperature and concentrated in vacuo. The crude dark oil was purified by flash chromatography (40 g silica gel, 0 to 8% methanol in chloroform) to afford the title compound (476 mg).

1. customequipped with a reflux condenser
2. customThen, the flask was evacuated
3. additionback-filled with nitrogen three times
4. additionbefore adding 1,4-dioxane (20 mL)
5. customThe resulting solution was sparged with nitrogen for 15 minutes
6. customlowered into an oil bath
7. waitto progress for another 24 h, at which point, analysis
8. customconsumption of the starting material and formation of the desired product
9. temperatureThe reaction was cooled to ambient temperature
10. concentrationconcentrated in vacuo
11. customThe crude dark oil was purified by flash chromatography (40 g silica gel, 0 to 8% methanol in chloroform)