反应详情

温度

90 °C

A stirred DMF (8.0 mL) solution of (R)-tert-butyl 4-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-3,3-dimethylpiperidine-1-carboxylate (1.20 g, 2.57 mmol), 6-methoxypyridin-3-ylboronic acid (0.787 g, 5.15 mmol), potassium phosphate (1.639 g, 7.72 mmol), palladium acetate (0.058 g, 0.257 mmol) and 1,1′-Bis(di-tert-butylphosphino)ferrocene (0.124 g, 0.257 mmol) was degassed by purging with argon for 5 min. The sealed tube was then heated at 90° C. for 1 h then cooled and partitioned between ethyl acetate and water. The layers were separated and the organic portion was washed with water, 10% LiCl (×2), brine and dried over anhyd. magnesium sulfate, filtered and concentrated under vacuum to afford the title compound as a tan solid (1.30 g, quantitative). HPLC (Method B) retention time=3.90 min. LCMS (m+1)=495.3. Material contained ˜10% of unreacted bromide starting material but was used without any further purification in next transformation.

1. customby purging with argon for 5 min
2. temperaturethen cooled
3. custompartitioned between ethyl acetate and water
4. customThe layers were separated
5. washthe organic portion was washed with water, 10% LiCl (×2), brine
6. customdried over anhyd
7. filtrationmagnesium sulfate, filtered
8. concentrationconcentrated under vacuum