Reaction Steps
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), 4-trifluoromethylbenzyl bromide (30 mg, 0.126 mmol), and 2M sodium carbonate (0.15 ml, 0.300 mmol) in toluene (2 ml), water (0.6 ml), and ethanol (0.25 ml) was added tetrakis(triphenylphosphine)palladium(0) (4 mg, 3.46 μmol). The mixture was microwaved at 100° C. in a sealed tube for 30 min, at which point LC/MS analysis showed a new peak at the product molecular weight. The organic phase of the reaction mixture was added directly to a 25 samplet and 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. This product was repurified by reverse-phase HPLC on a Kromasil C18 21×100 mm column, eluting at 15 ml/min with 90% water (0.1% TFA) to 95% acetonitrile (0.1% TFA) over 10 min, hold for 2 min, then back to 90% water over 0.5 min, hold for 0.5 min, to provide the title compound (9.4 mg, 0.017 mmol, 25.3% yield). Mass spectrum (ESI) 558.2 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=8.5 Hz, 2H); 7.93 (d, J=8.5 Hz, 2H), 7.93 (d, J=1.5 Hz, 1H); 7.53 (d, J=8.0 Hz, 2H), 7.51 (s, 1H), 7.27 (d, J=8.5 Hz, 1H), 6.28 (br t, J=5.5 Hz, 1H), 5.48 (br s, 1H), 3.47 (septet, J=7.0 Hz, 1H), 3.44 (br t, J=6.0 Hz, 2H), 3.32 (s, 1H), 2.24 (m, 1H), 1.80-1.98 (m, 7H), 1.46 (d, J=7.0 Hz, 6H), 1.30-1.42 (m, 2H).
