反应详情

温度

80 °C

A mixture of tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-azetanecarboxylate (0.15 g, 0.00036 mol), N-(5,7-dimethyl-1,3-benzoxazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.16 g, 0.00045 mol), tetrakis(triphenylphosphine)palladium (0.021 g, 0.000018 mol) and sodium carbonate (0.095 g, 0.0009 mol) in ethylene glycol dimethyl ether (5 mL) and water (2 mL) was heated at 80° C. for 16 hours under an atmosphere of nitrogen. The reaction was cooled to room temperature. Additional tetrakis(triphenylphosphine)palladium (0.021 g, 0.000018 mol) was added to the mixture. The reaction was stirred at 80° C. for 3 hours. The mixture was allowed to cool to ambient temperature, and the solvent was removed under the reduced pressure. The residue was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure to leave a brownish solid which was purified by flash column chromatography on silica using 5%-50% methanol t dichloromethane as a mobile phase to give tert-butyl 3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-azetanecarboxylate (0.033 g, 0.00006 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-95% acetonitrile-0.1 M ammonium acetate over 10 min, 1 mL/min) Rt 11.6 min. MS: MH+ 527.

1. temperatureThe reaction was cooled to room temperature
2. temperatureto cool to ambient temperature
3. customthe solvent was removed under the reduced pressure
4. customThe residue was partitioned between water and dichloromethane
5. extractionThe aqueous layer was extracted with dichloromethane (3×50 mL)
6. washThe combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine
7. dry with materialdried over magnesium sulfate
8. customThe solvents were evaporated under the reduced pressure
9. customto leave a brownish solid which
10. customwas purified by flash column chromatography on silica using 5%-50% methanol t dichloromethane as a mobile phase