METHOD FOR SYNTHESIS OF PERINDOPRIL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

摘要

Production of perindopril (I) comprising reacting optionally carboxy-protected (S)-2-bromophenylalanine (II) with N-((S)-1-ethoxycarbonylbutyl)-(S)-alanine (III) or ethyl (2S)-2-((4S)-4-methyl-2,5-dioxo-3-oxazolidinyl)pentanoate (IV), cyclizing the resulting amide (V) to give an indole derivative (VI), and catalytically hydrogenating (VI), is new. Production of perindopril of formula (I) comprises: (a) reacting optionally carboxy-protected (S)-2-bromophenylalanine of formula (II) with N-((S)-1-ethoxycarbonylbutyl)-(S)-alanine of formula (III) or ethyl (2S)-2-((4S)-4-methyl-2,5-dioxo-3-oxazolidinyl)pentanoate of formula (IV); (b) cyclizing the resulting amide of formula (V) to give an indole derivative of formula (VI); and (c) catalytically hydrogenating (VI). R = H or a protecting group. An Independent claim is also included for compounds (V).