Reaction Steps
To a dichloromethane (20 mL) solution of 2-butyl-4-chloro-1-{[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (1.76 g, 3.72 mmol), (2S)-6-hydroxyhexane-1,2-diyl dinitrate (intermediate 3, 0.83 g, 3.72 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.85 g, 4.46 mmol), and 1-hydroxybenzotriazole (0.68 g, 4.46 mmol) was added N-methylmorpholine (1.84 mL, 16.7 mmol), followed by N,N-dimethylaminopyridine (4.5 mg, 0.04 mmol). After 12 hours, the reaction mixture was washed with saturated sodium bicarbonate solution, brine, dried (magnesium sulfate), filtered, and concentrated in vacuo. Purification of the reaction mixture by reversed-phase mass-directed high-performance liquid chromatography afforded the title compound. 1H NMR (500 MHz, CD3CN) δ 7.69 (d, J=7.6 Hz, 1H), 7.64 (t, J=7.6 Hz, 1H), 7.53 (t, J=7.7 Hz, 1H), 7.50 (d, J=7.8 Hz, 1H), 7.10 (d, J=8.2 Hz, 2H), 7.03 (d, J=8.0 Hz, 2H), 5.63 (s, 2H), 5.34-5.41 (m, 1H), 4.83 (dd, J=2.5, 12.8 Hz, 1H), 4.58 (dd, J=6.2, 13.0 Hz, 1H), 4.25 (t, J=6.2 Hz, 2H), 2.78 (t, J=7.8 Hz, 2H), 1.79 (q, J=7.5 Hz, 2H), 1.71 (quintet, J=6.8 Hz, 2H), 1.48-1.60 (m, 4H), 1.28 (sextet, J=7.4 Hz, 2H), 0.83 (t, J=7.3 Hz, 3H); LC-MS: m/z 643 (M+H).
