反应详情

A solution of tert-butyl 7-(6-(4-aminophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (0.48 g, 0.92 mmol) in dichloromethane (15 mL) was treated with triethylamine (1.2 mL), followed by a solution of triphosgene (0.14 g, 0.46 mmol). After the passage of 5 minutes, a solution of 4-aminopyridine (0.26 g, 2.8 mmol) in warm tetrahydrofuran was added to the tert-butyl 7-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (“isocyanate”) mixture. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography using a Phenomenex Prodigy 21 mm×250 mm column, running a gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 65% acetonitrile to provide tert-butyl 7-(6-(4-(3-pyridin-4-ylureido)phenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate.hydrochloride as pale golden flakes. (282 mg, 45%). MS (ES+): 640.3 (M+H)+

1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
2. customThe residue was purified by reverse-phase high performance liquid chromatography
3. washa gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 65% acetonitrile