反应详情

The title compound was made in a similar way as that of the compound of example 89 from of 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one (intermediate D2a, 804 mg, 1.579 mmol) and 3-methoxy-5-(tributylstannyl)pyridine (1257 mg, 3.16 mmol) at 120° C. overnight. Solvent was removed, and product was purified by Biotage Si 25 g with a gradient of DCM and EtOH affording a as yellow pale solid (500 mg). This material was dissolved in dry DCM (10 mL), 1M BBr3 in DCM (24 ml) was added and the solution was stirred at room temperature for 48 hrs. Then, solution was cooled to 0° C. and dry ethanol (10 ml) was added. Solvent was evaporate and product was straightforward purified via reverse phase chromatography with a Biotage C18 SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%); (Phase B ACN 95%, water 5%, formic acid 0.1%) affording the title compound as white solid. Then, product was dissolved in a mixture of DCM (100 ml) and EtOH (5 ml) and the solution was washed with saturated solution of aqueous NaHCO3. aqueous phase was extracted with DCM (5×50 ml). Organic phases were collected, dried and solvent evaporated to dryness affording desired product affording the title compound (331 mg, 0.695 mmol, 68.4% yield) as a white solid.

1. customat 120° C.
2. customovernight
3. customSolvent was removed
4. customproduct was purified by Biotage Si 25 g with a gradient of DCM and EtOH affording a as yellow pale solid (500 mg)
5. dissolutionThis material was dissolved in dry DCM (10 mL)
6. addition1M BBr3 in DCM (24 ml) was added
7. temperatureThen, solution was cooled to 0° C.
8. additiondry ethanol (10 ml) was added
9. customSolvent was evaporate
10. customproduct was straightforward purified via reverse phase chromatography with a Biotage C18 SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%)