Process for the preparation of perindopril
A process for preparing perindopril is provided comprising condensing an N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of formula II: wherein X is a halide with an (2S,3aS,7aS)-2-carboxyperhydroindole of formula III: wherein R is hydrogen or a protecting group.
1 - 17 . (canceled)
18 . Perindopril erbumine prepared in accordance with a process comprising (a) condensing an N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of formula II:
wherein X is a halide with an (2S,3aS,7aS)-2-carboxyperhydroindole of formula III:
wherein R is hydrogen or a protecting group and converting the product of step (a) to perindopril erbumine having a purity of greater than or equal to about 95%.
19 . (canceled)
20 . The perindopril erbumine of claim 18 , wherein the step of condensing is carried out in one or more organic solvents and in the presence of a base.
21 . The perindopril erbumine of claim 20 , wherein the organic solvent is one or more anhydrous solvents.
22 . The perindopril erbumine of claim 21 , wherein the anhydrous solvent is a chlorinated hydrocarbon selected from the group consisting of dichloromethane, dichloroethane and mixtures thereof.
23 . The perindopril erbumine of claim 21 , wherein the anhydrous solvent is an aromatic hydrocarbon selected from the group consisting of benzene, toluene, and mixtures thereof.
24 . The perindopril erbumine of claim 21 , wherein the anhydrous solvent is an aliphatic hydrocarbon selected from the group consisting of hexane, heptane, and mixtures thereof.
25 . The perindopril erbumine of claim 21 , wherein the anhydrous solvent is a cycloaliphatic hydrocarbon selected from the group consisting of cyclopentane, cyclohexane and mixtures thereof.
26 . The perindopril erbumine of claim 18 , wherein R of Formula III is a protecting group of the formula Si(R 1 )(R 2 )(R 3 ), wherein R 1 , R 2 and R 3 are independently a straight or branched alkyl or aryl group having from 1 to about 25 carbon atoms.
27 . The perindopril erbumine of claim 18 , wherein step (b) comprises treating perindopril with tert-butylamine to provide perindopril erbumine.
28 . The perindopril erbumine of claim 18 , having purity greater than 99.5%.