Triethylamine → 2-Hydroxyethyl(4-{4-[(1r,4r)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2-trifluoroethyl)-1h-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate

Participants

Reaction Steps

A solution of 4-(4-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (62 mg, 0.16 mmol) in dichloromethane (2 mL) was treated with triethylamine (130 μL), followed by a solution of triphosgene (24 mg, 0.08 mmol) in dichloromethane (1 mL). After the passage of 5 minutes, the appropriate nucleophile—in the case, ethylene glycol (56 μL)—was added to the (1R,4R)-5-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane (“isocyanate”) mixture. After standing overnight at room temperature, 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 95% acetonitrile to provide 2-hydroxyethyl(4-{4-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate. MS (ES+): 479.2 (M+H)+

Provenance & Evidence