反应详情

温度

70 °C

5-(Methylsulfonyl)-indoline (Matrix Scientific, Columbia, S.C., USA; 30 mg, 0.15 mmol) and triethylamine (70 μL, 0.5 mmol) were added to a solution of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 45 mg, 0.133 mmol) in tetrahydrofuran (1 mL). The mixture was heated to reflux. No reaction had occurred after 2 h. The volatiles were evaporated. Dimethylformamide (1 mL) and cesium carbonate (250 mg, 0.77 mmol) were added. The mixture was heated at 70° C. overnight, then poured into saturated aqueous sodium bicarbonate, and extracted three times with ethyl acetate. The combined organic extracts were washed twice with water and once with brine, dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography eluting with ethyl acetate to give 4-[4-(5-methanesulfonyl-2,3-dihydro-indol-1-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (14 mg, 21%) as an off-white solid.

1. temperatureThe mixture was heated to reflux
2. customThe volatiles were evaporated
3. extractionextracted three times with ethyl acetate
4. washThe combined organic extracts were washed twice with water and once with brine
5. dry with materialdried (magnesium sulfate)
6. filtrationfiltered
7. customevaporated
8. custompurified by column chromatography
9. washeluting with ethyl acetate