Trifluoroacetic acid → HCID 57964941, compound

Participants

Reaction Steps

Trifluoroacetic acid (0.5 mL) was added to a solution of 4-[4-(2-methyl-pyridin-3-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Example 92; 50 mg, 0.12 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 30 min and then the solvents were evaporated using high vacuum. Dichloromethane (4 mL) was added to the residue, and then isobutyl chloroformate (available from Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 25 mg, 0.18 mmol) was added at room temperature, followed by triethylamine (80 mg, 0.79 mmol). The mixture was stirred overnight at room temperature and then water was added. The layers were separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were evaporated, and purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isobutyl ester (31 mg, 63%) as a powder. 1H NMR (300 MHz, CDCl3) δ 0.97 (d, 6H, J=6.5 Hz), 1.90-2.06 (m, 3H), 2.20-2.35 (m, 2H), 2.45 (s, 3H), 2.95-3.10 (m, 2H), 3.90 (d, 2H, J=6.3 Hz), 4.32-4.48 (m, 2H), 4.95-5.10 (m, 1H), 7.26-7.72 (m, 1H), 7.50-7.54 (m, 1H), 8.07 (s, 1H), 8.45-8.60 (m, 2H). Mass spectrum MH+=411. HRMS Calcd. For C21H27N6O3 (MH+): 411.2139. Found: 411.2138.

Provenance & Evidence