Cyclopropylamine → 1-cyclopropyl-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea

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Reaction Steps

A solution of 4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (30 mg, 0.074 mmol) in dichloromethane (1 mL) was treated with triethylamine (0.05 mL), followed by a solution of triphosgene (11 mg, 0.037 mmol) in dichloromethane (1 mL). After the passage of 5 minutes, the appropriate nucleophile—in the case, cyclopropylamine (17 mg, 0.30 mmol)—was added to the 8-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane (“isocyanate”) mixture. After being left 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 Gemini 21 mm×100 mm column, running a gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 60% or 75% acetonitrile over 30 minutes to provide 1-cyclopropyl-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea (15 mg, 41%). MS (ES+): 488.2 (M+H)+

Provenance & Evidence