1,1,1,3,3,3-hexafluoro-2-isocyanatopropane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of {3-piperazin-1-yl-1-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile (0.10 g, 0.20 mmol) in methylene chloride (5 mL, 80 mmol) was added. 0.21M 1,1,1,3,3,3-hexafluoro-2-isocyanatopropane in m-xylene (1.2 mL, 0.24 mmol) was added, followed by N,N-diisopropylethylamine (71 μL, 0.41 mmol). The reaction was stirred overnight. The reaction was rotovaped and ethyl acetate was added, washed with sat. NH4Cl (×2), sat. NaHCO3, and sat. NaCl. The extracts were dried and the solvent removed by rotary evaporation to give 164 mg of an orange oil. The crude oil was purified by column chromatography on 40 g silica gel using a gradient of 0-8% MeOH/DCM, 0-0.8% NH4Cl. The product was collected as 82 mg of a glass (59% yield). LCMS (M+1): 586. washed with sat. NH4Cl (×2), sat. NaHCO3, and sat. NaCl The extracts were dried the solvent removed by rotary evaporation