Tetrahydrofuran → 4-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester

Beteiligte Stoffe

Reaktionsschritte

Triphosgene (1.6 g, 5.5 mmol) was added in portions to a solution of 1,1,1-trifluoro-2-propanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 0.45 mL, 5 mmol) in a mixture of pyridine (0.48 mL, 6 mmol) and carbon tetrachloride (25 mL) under nitrogen. The solution was stirred at 60° C. for 5.5 h and then cooled using an ice bath. 1 M aqueous hydrochloric acid (4 mL) was added and then the mixture was diluted with water and the layers were separated. The organic layer was dried (sodium sulfate), and filtered to give approximately 20 mL of solution, of which 6 mL were used directly in the next reaction without further purification. The solution (6 mL) as added to a mixture of 4-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 250 mg, 0.5 mmol) in tetrahydrofuran (1 mL). Diisopropylethylamine (0.5 mL, 2.8 mL) was added slowly and the mixture was stirred for 10 min and then evaporated to dryness and chromatographed using a 30 mm×3″ column of silica gel, eluting with 66-75% 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-1-methyl-ethyl ester (72 mg, 28%) as a white solid.

Herkunft & Nachweise