Reaction Steps
To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(piperidin-4-ylmethyl)benzamide (20 mg, INTERMEDIATE 15) in 5 ml of dichloromethane was added 3-cyclohexylpropanoyl chloride (13 mg), and then diisopropylethylamine (450 μl). The reaction was stirred for 2 h at room temperature. The mixture was then diluted with 10 ml of ethyl acetate and 10 ml of water. The phases were separated and the aqueous phase was extracted with 10 ml of ethyl acetate. The combined organic phases were washed with 10 ml of brine, dried over Na2SO4, and concentrated. The residue was purified by reverse-phase HPLC on a Biotage Parallex Flex, 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 (12 mg, 36%). Mass spectrum (ESI) 541.3 (M+1). 1H NMR signals are doubled and broadened because of restricted rotation about the amide C—N bond. 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=8 Hz, 2H), 8.19 (s, 1H), 7.95 (d, J=8 Hz, 2H), 7.92 (d, J=1 Hz, 1H), 7.51 (s, 1H), 6.68-6.70 (m, 1H), 6.65 (m, 1H), 3.89-3.98 (m, 1H), 3.44-3.50 (m, 2H), 3.35 (m, 1H), 3.084 (m, 1H), 2.72 (s, 1H), 2.62 (m, 1H), 2.37-2.40 (m, 3H), 1.98 (m, 1H), 1.87 (m, 2H), 1.62-1.70 (m, 7H), 1.48 (m, 3H), 1.45 (d, J=7 Hz, 6H), 1.336 (d, H=7 Hz, 2H), 1.09-1.24 (m, 10H), 0.86-0.93 (m, 3H).
