反应详情

温度

75 °C

tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (126 mg, 0.998 mmol) was dissolved in 2-propanol (5 mL) and the solution was heated to 75° C. with a heating block. Then 2M HCl (2.5 mL) was added, the temperature was lowered to 65° C., and the reaction mixture was stirred for 3 h. The solution was concentrated and purified by preparatory HPLC eluting with water (10 mM NH4HCO3) and ACN/water (80/20 v/v, 10-50% gradient, 10 mM NH4HCO3) to give the title compound as a white solid (79 mg, 96%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.75-1.77 (m, 1H), 2.09-2.12 (m, 1H), 3.60-3.63 (m, 1H), 3.76-3.77 (m, 1H), 3.88-3.98 (m, 3H), 4.44 (d, J=6.35 Hz, 2H), 4.54-4.55 (m, 1H), 7.17 (d, J=5.86 Hz, 1H), 7.89 (br s, 1H), 8.54 (s, 1H), 8.58 (s, 1H), 9.43 (s, 1H). [M+H] calc'd for C16H17F3N6O2, 383. found, 383.

1. customwas lowered to 65° C.
2. concentrationThe solution was concentrated
3. custompurified by preparatory HPLC
4. washeluting with water (10 mM NH4HCO3) and ACN/water (80/20 v/v, 10-50% gradient, 10 mM NH4HCO3)