Trifluoroacetic acid → HCID 57965008, compound

Participants

Reaction Steps

A mixture of 4-[4-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Example 102; 120 mg, 0.28 mmol), trifluoroacetic acid (1.1 mL) and dichloromethane (5.5 mL) was stirred at room temperature for 30 min. The volatiles were evaporated under high vacuum and the residue was dissolved in dichloromethane (6 mL). Isopropyl chloroformate (1 M in toluene; 0.42 mL, 0.42 mmol) and triethylamine (254 μL, 1.8 mmol) were added and the mixture was stirred overnight at room temperature. 1 M aqueous sodium carbonate and dichloromethane were added, and the aqueous layer was extracted three times with dichloromethane. The combined organic extracts were evaporated and the residue was purified by column chromatography on silica gel, eluting with 0-4% methanol/dichloromethane, to give 4-[4-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (79 mg, 68%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.27 (d, 6H, J=6.0 Hz), 2.01 (d, 2H, J=10.9 Hz), 2.11-2.39 (m, 2H), 3.01 (t, 2H, J=12.8 Hz), 3.76 (s, 3H), 4.35 (br s, 2H), 4.85-5.06 (m, 2H), 7.07 (d, 1H, J=10.0 Hz), 7.23 (d, 1H, J=10.0 Hz), 8.17 (s, 1H), 8.51 (s, 1H). Mass spectrum (ES) MH+=414. HRMS Calcd. for C19H24N7O4 (MH+): 414.1885. Found: 414.1884.

Provenance & Evidence