Toluene → HCID 25122895, compound

Participants

Reaction Steps

Trifluoroacetic acid (3 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; 300 mg, 0.7 mmol) in dichloromethane (12 mL). The solution was stirred at room temperature for 30 min and then the solvents were evaporated, first using house vacuum and then high vacuum. Dichloromethane (10 mL) was added to the residue, and then a solution of isopropyl chloroformate in toluene (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 1 M; 1.1 mL, 1.1 mmol) was added at room temperature, followed by triethylamine (480 mg, 4.7 mmol). The mixture was stirred for 2 h 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 silica gel column chromatography, eluting with 0-80% ethyl acetate/hexanes) to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (291 mg, 100%) as a viscous oil. 1H NMR (300 MHz, CDCl3) δ 1.28 (d, 6H, J=6.4 Hz), 2.00-2.03 (m, 1H), 2.24-2.30 (m, 2H), 2.46 (s, 3H), 2.95-3.04 (m, 2H), 4.27-4.39 (m, 2H), 4.93-5.00 (m, 2H), 7.28-7.32 (m, 1H), 7.52-7.55 (m, 1H), 8.07 (s, 1H), 8.48-8.52 (m, 2H). Mass spectrum MH+=397. HRMS Calcd. For C20H25N6O3 (MH+): 397.1983. Found: 397.1982.

Provenance & Evidence