ACE-inhibiting substituted alanyl-derivatives of e.g. proline preparation

摘要

Preparation of ACE inhibiting compounds of formula Z(CH2)2CH(COOEt)NHCHMeCOR1 (I) and their salts comprises reaction of Z(CH2)2CH(COOEt)NHCHMeCOOH (II) with a silylating agent (so as to introduce a trimethylsilyl protecting group) in an organic, water-free solvent, and optionally in the presence of a base, to obtain Z(CH2)2CH(COOEt)N(SiMe3)CHMeCOOSiMe3 (III), followed by reaction at -50 to -10 deg C to produce Z(CH2)2CH(COOEt)N(SiMe3)CHMeCOCl (IV), which is then reacted with R1H (where the carboxyl group in R1 may be protected), and optionally deprotection, to give (I). Z = alkyl, aryl or heterocyclyl (preferably Ph); R1 = an amine of formula (a)-(k).