反应详情

To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-{[trans-4-(2-hydroxyethyl)cyclohexyl]methyl}benzamide (50 mg, 0.112 mmol, EXAMPLE 43, Step A) and 1,1′-(azodicarbonyl)dipiperidine (57 mg, 0.226 mmol) in toluene (2 ml) was added tri-n-butylphosphine (0.06 ml, 0.241 mmol). After stirring for 10 min, hexafluoro-2-methylisopropanol (0.03 ml, 0.245 mmol) was added. Tetrahydrofuran (2 ml) was added to solubilize starting material, and the mixture was stirred overnight at room temperature. The mixture was concentrated and the residue was 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 (8.7 mg, 0.014 mmol, 12.72% yield). Mass spectrum (ESI) 610.2 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.33 (d, J=8.5 Hz, 2H); 7.94 (d, J=8.5 Hz, 2H), 7.94 (d, J=1.5 Hz, 1H); 7.51 (s, 1H), 6.27 (br s, 1H), 3.72 (t, J=6.5 Hz, 2H), 3.46 (septet, J=6.5 Hz, 1H), 3.36 (t, J=6.0 Hz, 2H), 1.83 (m, 4H), 1.50-1.65 (m, 5H), 1.46 (d, J=7.0 Hz, 6H), 1.40-1.50 (m, 2H), 0.85-1.22, (m, 6H).

1. stirringthe mixture was stirred overnight at room temperature
2. concentrationThe mixture was concentrated
3. customthe residue was purified by flash chromatography on a Biotage Horizon, 25S column
4. washeluting with 1 column volume of 100% dichloromethane