Pyridine → HCID 57964951, compound

Participants

Reaction Conditions

Reaction Steps

Triphosgene (1.6 g, 5.5 mmol) was added to a solution of 2,2,2-trifluoroethanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 500 mg, 5 mmol) in pyridine (6 mmol) and carbon tetrachloride (25 mL). The mixture was heated to 60° C. for 6 h, then cooled and washed with 1 M aqueous hydrochloric acid. The organic layer was dried (magnesium sulfate), filtered, and evaporated carefully using a cold rotary evaporator bath. The resulting material was suspended in dichloromethane (10 mL) and 4-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 200 mg, 0.41 mmol) and diisopropylethylamine (350 μL, 2 mmol) were added. The mixture was stirred for 15 min and then purified by column chromatography, eluting with 50% ethyl acetate/hexanes, to give 4-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-ethyl ester (71 mg, 35%) as a yellow powder.

Provenance & Evidence