反应详情

To a microwave safe vial was added Intermediate 39 (375 mg, 1.77 mmol), 2-chloro-6-methylpyridine (0.39 mL, 3.53 mmol), CH3CN (10 mL) and DIPEA (0.61 mL, 3.53 mmol). The resulting mixture was heated to 180 C in a microwave reactor. After 3 h the crude mixture was concentrated and purified directly by FCC (SiO2, ethyl acetate/hexanes, 0-40%) to yield (1R,6S)-tert-butyl 8-(6-methylpyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate (80 mg, 15%). MS (ESI) mass calcd. for C17H25N3O2, 303.2; m/z found, 304.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.31 (t, J=7.7 Hz, 1H), 6.50-6.40 (m, 1H), 6.09 (dd, J=45.4, 8.1 Hz, 1H), 4.44-4.27 (m, Hz, 2H), 4.04-3.89 (m, 1H), 3.84-3.66 (m, 2H), 3.60-3.22 (m, 2H), 2.86-2.72 (m, 1H), 2.37 (s, 3H), 2.07-1.96 (m, 1H), 1.92-1.80 (m, 1H), 1.44-1.28 (m, 9H).

1. temperatureThe resulting mixture was heated to 180 C in a microwave reactor
2. concentrationAfter 3 h the crude mixture was concentrated
3. custompurified directly by FCC (SiO2, ethyl acetate/hexanes, 0-40%)