반응 단계
A mixture of 2-butyl-4-chloro-1-{[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (Step A, Intermediate 4, 7.83 g, 16.5 mmol), isosorbide-5-mononitrate (1.55 g, 8.11 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.78 g, 19.7 mmol), 1-hydroxybenzotriazole (1.25 g, 8.16 mmol), 4-dimethylaminopyridine (0.10 g, 0.82 mmol), and N-methylmorpholine (9.0 mL, 82 mmol) was dissolved in dichloromethane (150 mL) and stirred for 2 days. It was then concentrated in vacuo and purified by reversed-phase mass-directed HPLC (Sunfire C-18) to afford the title compound. 1H NMR (500 MHz, CDCl3) δ 8.02 (dd, J=7.6, 1.0 Hz, 1H), 7.61 (td, J=7.6, 1.3 Hz, 1H), 7.55 (td, J=7.7, 1.1 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.18 (d, J=7.7 Hz, 2H), 6.96 (d, J=7.8 Hz, 2H), 5.50 (s, 2H), 5.40 (td, J=5.4, 3.0 Hz, 1H), 5.32-5.30 (m, 1H), 4.99 (t, J=5.2 Hz, 1H), 4.51 (d, J=5.0 Hz, 1H), 4.06-4.02 (m, 3H), 3.99 (dd, J=11.4, 5.4 Hz, 1H), 2.68 (t, J=7.7 Hz, 2H), 1.69 (quintet, J=7.7 Hz, 2H), 1.36 (sextet, J=7.5 Hz, 2H), 0.89 (t, J=7.3 Hz, 3H); LC-MS: m/z 610.1 (M+H).
