1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Tert-Butyl(3R,4S)-3-{[[3-{[(1R,2R)-2-({[(5R)-5,6-bis(nitrooxy)hexyl]oxy}-carbonyl)cyclopropyl]methoxy}-5-(3-methoxypropyl)benzyl](cyclopropyl)amino]-carbonyl}-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of (1R,2R)-2-{[3-{[[((3R,4S)-1-(tert-butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)-amino]methyl}-5-(3-methoxypropyl)phenoxy]methyl}cyclopropanecarboxylic acid (1 eq.) from Example 4/Step 1 in DCM (0.17 M) was added (2R)-6-hydroxyhexane-1,2-diyl dinitrate (1.5 eq., prepared according to the procedure described in WO2005070868/Example 2, incorporated by reference), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.5 eq.), and 4-dimethylaminopyridine (1.5 eq.). The reaction was stirred at rt for 18 h and then concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 40% EtOAc in Hex) to afford the title compound as an oil.

Provenance & Evidence