Hydrochloric Acid → 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

Triphosgene (217 mg, 0.73 mmol) was added to a solution of (R)-(−)-2-butanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 148 mg, 2 mmol) in a mixture of pyridine (190 μL, 2.3 mmol) and 1,2-dichloroethane (10 mL). The solution was stirred at 40° C. for 3 h and then cooled to room temperature. 1 M aqueous hydrochloric acid (2.5 mL) and water (3 mL) were added. The layers were separated and the organic phase was dried (magnesium sulfate), filtered, and evaporated. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 220 mg, 0.45 mmol) and diisopropylethylamine (250 μL) were added and the mixture was stirred for 30 min and then chromatographed, eluting with 50-75% ethyl acetate/hexanes, to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester (78 mg, 36%) as an off-white foam/solid.

Herkunft & Nachweise