反应详情

温度

80 °C

In a 1 L single necked flask were charged 4-[6-chloro-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (21.3 g, 37 mmol), anhydrous tetrahydrofuran (370 ml), and tributyl(vinyl)stannane (11.9 ml, 40.7 mmol). The mixture was degassed for 15 minutes using argon, dichlorobis(triphenylphosphine)palladium (1.3 g, 1.8 mmol) was then added. The resulting solution was heated at 80° C. overnight under argon, then evaporated under reduced pressure. Ethyl acetate and a 5% aqueous potassium fluoride solution were added to the residue, the resulting precipitate was filtered. The filtrate was recovered and the two layers separated, the organic phase was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The crude product was purified on a silica gel column chromatography using a gradient of ethyl acetate (0-40%) in cyclohexane to afford the title compound as a brown foam (12.3 g, 70%).

1. customThe mixture was degassed for 15 minutes
2. additionwas then added
3. customevaporated under reduced pressure
4. additionEthyl acetate and a 5% aqueous potassium fluoride solution were added to the residue
5. filtrationthe resulting precipitate was filtered
6. customThe filtrate was recovered
7. customthe two layers separated
8. washthe organic phase was washed with water
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customThe crude product was purified on a silica gel column chromatography