反应详情

3-(3-Fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (intermediate G1, 0.135 g, 0.521 mmol) and potassium carbonate (0.206 g, 1.498 mmol) were mixed in DMF (5 ml) and stirred at r.t. for 10 min. Then a solution of 3-(1-bromoethyl)-4-(morpholinomethyl)-1H-isochromen-1-one hydrobromide (intermediate C48, 0.215 g, 0.496 mmol) in DMF (5 ml) was added and the mixture was heated at 70° C. for 3 hrs. The reaction was quenched by the addition of 1M HCl (2 ml) and the solvent was removed under vacuum. The crude was purified by reverse phase flash chromatography on C18 Biotage cartridge (H2O:CH3CN=80:20 to 100% CH3CN, with 0.1% HCOOH) to afford 3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(morpholinomethyl)-1H-isochromen-1-one (0.033 g).

1. temperaturethe mixture was heated at 70° C. for 3 hrs
2. customThe reaction was quenched by the addition of 1M HCl (2 ml)
3. customthe solvent was removed under vacuum
4. customThe crude was purified by reverse phase flash chromatography on C18 Biotage cartridge (H2O:CH3CN=80:20 to 100% CH3CN, with 0.1% HCOOH)