Procedure for the synthesis of perindopril and its pharmacologically acceptable salts i2003/26

摘要

Process for the industrial synthesis of perindopril (I) and its salts, by reaction of a hexahydroindole carboxylic ester (II) with an amino acid halide (III) in the S configuration, to form, after removal of protecting groups, a (S) N-substituted hexahydroindole (IV), reacting this with an (R) ester (V) in the presence of a base to form a perindopril ester (VI) and hydrogenating this in the presence of a catalyst to give (I). Process for the industrial synthesis of perindopril (I) and its salts, by reaction of a hexahydroindole carboxylic ester (II) with an amino acid halide (III) in the S configuration, in the presence of a base to form, after removal of protecting groups, a (S) N-substituted hexahydroindole (IV) and reacting this with an (R) ester (V) in the presence of a base to form a perindopril ester (VI), then hydrogenating this in the presence of a palladium, platinum, rhodium or nickel catalyst to give, after removal of protecting groups if necessary, the compound of formula (I). R1 = H, benzyl or 1-6C alkyl; X = halogen; R2 = a group protecting the amino group; and G = Cl, Br, I, p-toluene sulfonyloxy, methane sulfonyloxy, or trifluoromethane sulfonyloxy.