Ramipril, Hoe-498, Carasel, Altace, Delix, Ramace, Unipril, Tritace, Triatec

雷米普利Chemical Name: (2S,3aS,6aS)-1-[N-[1(S)-(Ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]octahydrocyclopenta[b]pyrrole-2-carboxylic acid; 1-[N-[1(S)-(Ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-(1S,5S)-2-azabicyclo[3.3.0]octane-3(S)-carboxylic acid
CAS No. 87333-19-5
项目整合开发状态: Launched-1989
项目研究机构: Aventis Pharma (Originator), Almirall Prodesfarma (Licensee), AstraZeneca (Licensee), King Pharmaceuticals (Licensee), Zambon (Licensee), SkyePharma (Codevelopment)
合成路线:The reaction of 1-cyclopentenylpyrrolidino (I) with methyl 2-acetylamino-3-chloropropionate (II) in DMF gives methyl 2-acetylamino-3-(2-oxocyclopentyl)propionate (III),which is cyclized in refluxing concentrated HCl and reduced with H2 over Pd/C in acetic acid yielding cis,endo-2-azabicyclo[3.3.0]octan-3-carboxylic acid (IV).Esterification of (IV) with SOCl2 and benzyl alcohol affords the corresponding benzyl ester (V),which is condensed with N-(1-ethoxycarbonyl-3-phenylpropyl)alanine (VI) by means of dicyclohexylcarbodiirnide (DCC) in DMF affording benzyl N-(1-ethoxycarbonyl-3-phenylpropyl)alanyl-cis,endo-2-azabicyclo[3.3.0]octan-3-carboxylate (VII).Finally,this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol.