反应详情

温度

60 °C

A mixture of 4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-[1-methyl-5-(piperidin-3-yl)-1H-pyrazol-4-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1 (14),2,4,10,12-pentaene (100 mg, 0.21 mmol), ethyl 2-bromo-2-methylpropanoate (348.6 mg, 2.100 mmol), Ag2O (487.2 mg, 2.100 mmol), H2O (0.5 mL), and CH3CN (1.5 mL) in a seal tube was heated at 60° C. for 8 h. The solid was filtered off and the filtrate was purified by Combiflash eluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3 to afford racemic 252 (35 mg, 30% yield), which was separated by chiral SFC (AS-H column, 0.1% DEA in MeOH isocratic) to give: 5.0 mg of one enantiomer and 3 mg of the other (7% total yield). LCMS (ESI): RT=5.19 min, m/z: 558.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.42 (d, J=8.0 Hz, 1H), 7.91 (s, 1H), 7.09-7.07 (m, 1H), 7.02-6.94 (m, 3H), 5.86-5.83 (m, 1H), 4.52 (s, 4H), 3.89 (s, 3H), 2.74-2.63 (m, 2H), 2.37-2.32 (m, 2H), 2.26 (s, 3H), 2.00 (s, 1H), 1.75-1.60 (m, 3H), 1.47-1.45 (m, 6H), 1.02-0.97 (m, 7H)

1. filtrationThe solid was filtered off
2. customthe filtrate was purified by Combiflash
3. washeluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3