Process for the preparation of intermediates of trandolapril and use thereof for the preparation of trandolapril
AssigneeGlenmark Pharmaceuticals S.A.
InventorsNarendra Joshi, Shekhar Bhirud, Buddhavarapu Ramam, Arjun Bodkhe
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Abstract
A process for the preparation of an intermediate of trandolapril, (2S,3aR,7aS)-perhydroindole-2-carboxylic acid of Formula II is provided. Also provided are processes for preparing trandolapril.
Claims39
A process for the preparation of an intermediate of trandolapril, (2S,3aR,7aS)-perhydroindole-2-carboxylic acid of Formula II:
- the process comprising:
- (a) esterifying (3aR,7aS)-perhydroindole-2-carboxylic acid of Formula III:
- with an alcohol of the formula ROH wherein R is an aliphatic, aryl or aralkyl group and a suitable acid to provide an acid addition salt of the compound of Formula IV:
- wherein R has the aforestated meanings;
- (b) reacting the acid addition salt of the compound of Formula IV with a first base to provide a compound of Formula V:
- (c) reacting the compound of Formula IV with dibenzoyl-L-tartaric acid or di-p-toluoyl-L-tartaric acid and at least one alcohol of the formula R1OH wherein R1 is an alkyl group containing from 1 to about 12 carbon atoms, and adding a second base to precipitate a compound of Formula VI:
- (d) hydrolyzing the compound of Formula VI to provide the compound of Formula II.
A process for the preparation of trandolapril comprising:
- (a) reacting N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine and N,N′-carbonyldiimidazole in the presence of a solvent to form an N-carboxyanhydride;
- and
- (b) reacting the N-carboxyanhydride with (2S,3aR,7aS)-perhydroindole-2-carboxylic acid to provide trandolapril.
A process for preparing trandolapril comprising reacting a N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of Formula X:
- Me
- wherein X is a halide and Ph is phenyl with (2S,3aR,7aS)-perhydroindole-2-carboxylic acid of Formula II:
- in the presence of a base to provide trandolapril.
A process for preparing trandolapril comprising reacting (2S,3aR,7aS)-perhydroindole-2-carboxylic acid of Formula II:
- with a trialkyl or aryl silyl halide in the presence of a first base and in situ reacted with a N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of Formula X:
- wherein X is a halide and Ph is phenyl in an organic solvent and in the presence of a second base followed by treatment with a suitable acid to obtain trandolapril.
Dependencies are inferred from the claim text.