反应详情

温度

160 °C

To a solution of 12-chloro-4-(pyridin-2-yl)-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (200 mg, 0.671 mmol) in NMP (10 mL) was added TEA (10 mL) and 1-(pyrrolidin-2-ylmethyl)piperidine (135 mg, 0.804 mmol). The reaction mixture was stirred at 160° C. for 24 h. After cooling to room temperature, the reaction mixture was purified by Combi-flash eluting with a 5-95% gradient of CH3CN in 0.3% NH4HCO3 to give 129 which was further purified by chiral HPLC (AS-H column, 10% EtOH isocratic) to separate 15.9 mg of one enantiomer and 7 mg of the other (8% total yield). LCMS (ESI): RT=4.55 min, m/z: 431.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.50-8.49 (d, J=4.0 Hz, 1H), 7.97-7.95 (d, J=8.0 Hz, 1H), 7.82-7.78 (m, 2H), 7.22-7.19 (m, 1H), 5.95 (s, 1H), 4.49-4.44 (m, 4H), 4.17 (m, 1H), 3.46-3.44 (m, 1H), 3.28-3.25 (m, 1H), 2.54 (m, 1H), 2.45-2.33 (m, 3H), 2.21-2.16 (m, 1H), 2.01-1.97 (m, 2H), 1.94-1.86 (m, 2H), 1.53-1.50 (m, 4H), 1.39-1.38 (m, 2H)

1. temperatureAfter cooling to room temperature
2. customthe reaction mixture was purified by Combi-flash
3. washeluting with a 5-95% gradient of CH3CN in 0.3% NH4HCO3