Process for the preparation of perindopril

• US 20080071094A1
• Filed: 09/21/2007
• Published: 03/20/2008
• Est. Priority Date: 03/21/2005
• Status: Abandoned Application

• Current Assignee: Glenmark Generics Limited (Glenmark Pharmaceuticals Limited)
• Original Assignee: Glenmark Pharmaceuticals Limited
• Inventors: BHIRUD, Shekhar, RAO, Kodali, SONI, Vijay, JOSHI, Narendra, RAMAM, Buddhavarapu
• Application Number:
  US11/903,352
• Publication Number:
  US 20080071094A1
• Time in Patent Office: Days
• US Class Current: 548/452
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

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.

Claims

1-17. -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:

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(R¹)(R²)(R³), wherein R¹, R² and R³ 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%.

19. (canceled)