Benzyl isocyanate → HCID 25171446, compound

Participants

Reaction Steps

To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(piperidin-4-ylmethyl)benzamide (30 mg, 0.075 mmol, INTERMEDIATE 15) in dichloromethane (1 ml) was added benzyl isocyanate (10 μl 0.081 mmol). The mixture was stirred for 2 h at room temperature, at which point LC/MS analysis showed a new peak at the desired molecular weight. The reaction mixture 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. The resulting mixture was repurified by reverse-phase HPLC: 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 (7.9 mg, 0.015 mmol, 19.79% yield). Mass spectrum (ESI) 536.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=7.0 Hz, 2H), 7.94 (d, J=7.0 Hz, 2H), 7.93 (d, J=1.5 Hz, 1H), 7.52 (s, 1H), 7.27-7.35 (m, 4H), 6.55 (br s, 1H), 4.43 (s, 2H), 3.99 (br d, J=11.0 Hz, 2H), 3.47 (septet, J=5.5 Hz, 1H), 3.42 (t, J=5.5 Hz, 2H), 2.86 (br t, J=10.5 Hz, 2H), 2.73 (s, 3H), 1.90 (m, 1H), 1.81 (br d, J=10.0 Hz, 2H), 1.46 (d, J=5.5 Hz, 6H), 1.31 (m, 2H).

Provenance & Evidence