Delapril hydrochloride, REV-6000A, CV-3317, Delaket, Cupressin, Adecut-药物合成数据库

【药物名称】Delapril hydrochloride, REV-6000A, CV-3317, Delaket, Cupressin, Adecut

化学结构式(Chemical Structure):

参考文献No.	46463
标题:	Bicyclic compounds, their production and use
作者:	Oka, Y.; Nishikawa, K.; Miyake, A. (Takeda Chemical Industries, Ltd.)
来源:	EP 0051391; GB 2086393; JP 82179141; JP 8277651; US 4385051

合成路线图解说明: 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.

合成路线图解说明: 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.

参考文献No.	65750
标题:	CV-3317
作者:	Serradell, M.N.; Casta馿r, J.
来源:	Drugs Fut 1984,9(5),324

合成路线图解说明: 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.

合成路线图解说明: 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.