反应详情

To a mixture of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl]methyl}benzamide (70 mg, 0.133 mmol, INTERMEDIATE 9), 2-bromo-5-(trifluoromethyl)pyridine (45 mg, 0.199 mmol), and cesium carbonate (130 mg, 0.400 mmol) in tetrahydrofuran (6 ml) and water (0.6 ml) was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (7 mg, 8.57 mmol). The mixture was heated to reflux and stirred at this temperature overnight. The reaction mixture was cooled and added directly to a 25 samplet, and then purified by flash chromatography on a Biotage Horizon, 25S column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 100% ethyl acetate in dichloromethane over 10 column volumes, to provide the title compound (35 mg, 0.064 mmol, 48.2% yield). Mass spectrum (ESI) 545.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.80 (s, 1H), 8.34 (d, J=8.5 Hz, 2H); 7.97 (d, J=8.5 Hz, 2H), 7.94 (d, J=1.0 Hz, 1H); 7.85 (d, J=8.0 Hz, 1H), 7.52 (s, 1H), 7.48 (d, J=8.5 Hz, 1H), 6.83, (br s, 1H), 6.37 (br t, J=5.5 Hz, 1H), 3.54 (br t, J=4.5 Hz, 2H), 3.48 (septet, J=6.5 Hz, 1H), 2.75 (br d, J=16.5 Hz, 1H), 2.53 (br d, J=15.5 Hz, 2H), 2.04-2.16 (m, 3H), 1.50-1.68 (m, 3H), 1.46 (d, J=7.0 Hz, 6H), 1.25 (m, 2H).

1. temperatureThe mixture was heated
2. temperatureto reflux
3. temperatureThe reaction mixture was cooled
4. additionadded directly to a 25 samplet
5. custompurified by flash chromatography on a Biotage Horizon, 25S column
6. washeluting with 1 column volume of 100% dichloromethane