Delapril hydrochloride, REV-6000A, CV-3317, Delaket, Cupressin, Adecut

盐酸地拉普利 地拉普利 Chemical Name: (S)-N-(2,3-Dihydro-1H-inden-2-yl)-N-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]glycine monohydrochloride; N-[N-[1-(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-N-(indan-2-yl)glycine monohydrochloride; (S)-2-[[(S)-1-[(Carboxymethyl)-2-indanylcarbamoyl]ethyl]amino]-4-phenylbutyric acid ethyl ester monohydrochloride
CAS No. 83435-67-0, 83435-66-9 (free base), 83435-62-5 (monoHBr)
项目整合开发状态: Launched-1989
项目研究机构: Takeda (Originator), Chiesi (Licensee)
合成路线:The reductocondensation of ethyl glycinate (I) with 2-indanone (II) by means of sodium cyanoborohydride in methanol gives ethyl N-(2-indanyl)glycinate (III),which is condensed with N-benzyloxycarbonyl-L-alanine (IV) by means of isobutyl chlorocarbonate and triethylamine in THF yielding N-(N-benzyloxycarbonyl-L-alanyl)-N-(2-indanyl)glycine ethyl ester (V).The partial hydrolysis of (V) with NaOH in methanol affords N-(N-benzyloxycarbonyl-L-alanyl)-N-(2-indanyl)glycine (VI),which is deprotected by hydrogenolysis with H2 over Pd/C in ethanol giving N-(L-alanyl)-N-(2-indanyl)glycine (VII).Finally,this compound is reductocondensed with ethyl 2-oxo-4-phenylbutanoate (VIII) by means of sodium cyanoborohydride in ethanol.

合成路线:The reductocondensation of (II) with tert-butyl glycinate (IX) by means of sodium cyanoborohydride in ethanol gives tert-butyl-N-(2-indanyl)glycinate (X),which is condensed with (IV) by means of isobutyl chlorocarbonate as before yielding tert-butyl-N-[N-(tert-butoxycarbonyl)-L-alanyl]-N-(2-indanyl)glycinate (XI).Deprotection of (XI) by hydrogenolysis with H2 over Pd/C in methanol affords tert-butyl N-(L-alanyl)-N-(2-indanyl)glycinate (XII),which is reductocondensed with (VIII) using H2 and Raney-Ni in ethanol to afford tert-butyl N-[N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-N-(2-indanyl)glycinate (XIII).Finally,this compound is saponified with HBr in acetic acid.