Novel method for the synthesis of perindopril and the pharmaceutically-acceptable salts thereof

摘要

Industrial synthesis of perindopril (I) and its salts by reaction of hexahydroindole carboxylic ester (II) with amino acid halide (III) to form N-substituted hexahydroindole (IV) and reacting with ethyl 2-oxo pentanoate under hydrogen in presence of platinum on charcoal catalyst to form perindopril ester (V) and removing the ester group to form (I) is new. Process for industrial synthesis of perindopril of formula (I) and its salts comprises reaction of a hexahydroindole carboxylic ester of formula (II) with an amino acid halide of formula (III) in the presence of a base, removing the protecting group to form an N-substituted hexahydroindole of formula (IV) and reacting this with ethyl 2-oxopentanoate under pressure of hydrogen and in the presence of a platinum on charcoal catalyst to form a perindopril ester of formula (V) and finally removing the ester group to form (I). R1 = benzyl or 1-6C alkyl; X = halogen; and R2 = amino protecting group.