反应详情

3-(6-chloro-1-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (3.08 g, 10.5 mmol) was dissolved in toluene (95 mL) and ethanol (55 mL). 4-Aminophenylboronic acid, pinacol ester (2.53 g, 11.55 mmol) was added followed by the addition of a 2M aqueous solution of Na2CO3 (21 mL). The mixture was degassed by bubbling a stream of nitrogen through the solution and tetrakis(triphenylphosphine)palladium (606 mg) was added. The mixture was heated under reflux for 16 h, cooled to room temperature and concentrated. The mixture was dissolved in ethyl acetate and washed with brine. The organic phase was dried over MgSO4 and filtered over magnesol. The aqueous phase was extracted with ethyl acetate, which was dried over MgSO4. The combined organic phases were concentrated. The crude product was applied to a silica gel column and eluted with ethyl acetate in hexanes (30-100%) to give 3.6 g of the title compound. HRMS: 351.1925 [M+H]. For [M+H]+ mass error=−0.3 mDa or −0.92 ppm.

1. customThe mixture was degassed
2. customby bubbling a stream of nitrogen through the solution and tetrakis(triphenylphosphine)palladium (606 mg)
3. additionwas added
4. temperatureThe mixture was heated
5. temperatureunder reflux for 16 h
6. concentrationconcentrated
7. dissolutionThe mixture was dissolved in ethyl acetate
8. washwashed with brine
9. dry with materialThe organic phase was dried over MgSO4
10. filtrationfiltered over magnesol
11. extractionThe aqueous phase was extracted with ethyl acetate, which
12. dry with materialwas dried over MgSO4
13. concentrationThe combined organic phases were concentrated
14. washeluted with ethyl acetate in hexanes (30-100%)