- AN IMPROVED PROCESS FOR PREPARATION OF PERINDOPRIL INTERMEDIATE
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The present invention relates to an improved process for the preparation of (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-lH-indole-2-carboxylic acid benzyl ester( the compound of formula II) comprising reacting (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acid phenylmethyl ester 4-methylbenzenesulfonate (the compound of formula III) with N-[(S)-ethoxycarbonyl-1-butyl]-(S)-alanine (the compound of formula IV), using 1-hydroxybenzotriazole (HOBT), dicyclohexylcarbodiimide (DCC) and triethylamine in the presence of toluene as a solvent at a temperature of 5°C to 40°C.
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Page/Page column 9; 13; 14
(2014/05/07)
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- PROCESS FOR THE PREPARATION OF PERINDOPRIL ERBUMINE SALT AND NOVEL POLYMORPH (S) THEREOF
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A single pot process for the preparation of perindopril erbumine salt according to which condensation of (2S, 3aS, 7aS)-octahydroindole-2-carboxylic acid benzyl ester para toluene sulfonate with N-((S-)-ethoxy carbonyl -1-ethyl-(S)-alanine, catalytic hydrogenation of benzyl ester of (2S, 3aS, 7aS)-1-{2-[1-(ethoxycarbonyl)-(S)-butylamino]-(S)propionyl}- octahydro-indole-2-carboxylate and conversion of (2S,3aS, 7aS)-1-{2-[1-ethoxycarbonyl)_(S)-butylamino]-(S)-propionyl}octahydroindole-2-carboxylic acid to its perindopril erbumine salt are carried out in a single pot using a single solvent such as isopropyl acetate to obtain perindopril erbumine salt of very high purity. Also a novel polymorph S of perindopril erbumine having X-ray diffraction peaks of 9.10, 14.64, 15.37, 16.58, 17.39, 19.99, 20.62, 21.50, 22.15, 22.60, 24.20, 27.55 ± 0.2 at 2Θ values. Also processes for preparing the novel polymorph S.
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Page/Page column 12
(2008/12/07)
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- PROCESS FOR THE PREPARATION OF N-[1-(S)-ETHOXYCARBONYL-1-BUTYL]-(S)-ALANINE-DMT COMPLEX AND ITS USE IN THE PREPARATION OF PERINDOPRIL
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A compound N-[l-(S)-ethoxycarbonyl-l-butyl]-(S)-alanine-DMT complex of Formula (II) is provided. Also provided is a process for the preparation of N-[l-(S)-ethoxycarbonyl-l-butyl]-(S)- alanine-DMT complex and its use in preparing perindopril or a pharmaceutically acceptable salt thereof.
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Page/Page column 10-11
(2008/06/13)
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- PROCESS FOR THE SYNTHESIS OF PERINDOPRIL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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A process for the synthesis of perindopril of formula (I): and its pharmaceutically acceptable salts.
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Page/Page column 2
(2008/06/13)
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- Process for the synthesis of perindopril and pharmaceutically acceptable salts thereof.
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Process for the industrial synthesis of perindopril of formula (I): and pharmaceutically acceptable salts thereof.
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Page/Page column 2
(2010/11/26)
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- PROCESS FOR THE PREPARATION OF CRYSTALLINE PERINDOPRIL
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The present invention relates to a new process for the preparation of crystalline perindopril. The present invention also relates to new alkyl ammonium salts of perindopril and the processes for the preparation thereof.
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Page/Page column 13
(2008/06/13)
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- Novel method for the synthesis of perindopril and the pharmaceutically acceptable salts thereof
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Process for the synthesis of perindopril of formula (I): and its pharmaceutically acceptable salts.
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Page/Page column 2
(2008/06/13)
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- Process for for synthesis of (2S,3aS,7aS)-1-(S)-alanyl-octahydro-1H-indole-2- carboxylic acid derivatives and use in the synthesis of perindopril
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The present invention relates to a compound of general formula IVA, wherein R is selected from substituted or unsubstituted arylalkyl groups; and HA represents an acid capable of forming a salt.
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Page/Page column 7
(2008/06/13)
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- Process for making (2S, 3aS, 7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl) butyl] amino]-1-oxopropyl] octahydro-1H-indole-2-carboxylic acid
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The present invention discloses a process for the synthesis and isolation of (2S, 3aS, 7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl] octahydro-1H-indole-2-carboxylic acid and its tert-butylamine salt, by condensing (2S, 3aS, 7aS)-octahydroindole-2-carboxylic acid benzyl ester and N[(S)1-carboxybutyl]-(S)-alanine ethyl ester in nonreactive solvents in turn avoiding the formation of impurity viz. N-acetyl (2S,3aS,7aS)-octahydroindole-2-carboxylic acid benzyl ester (Formula V). The de-protection of benzyl ester group is optimized and then isolation of the product from aqueous layer by extraction using an organic solvent, which eliminates the need of lyophilization. The process of the present invention yields perindopril erbumnine salt of Formula 1B free of contaminants derivable from dicyclohexylcarbodiimide and impurities originated by the use of ethyl acetate.
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Page/Page column 4
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF PERINDOPRIL
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The present invention provides an improved process for the preparation of Perindopril of Formula (I) and its pharmaceutically acceptable salts.
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Page/Page column 7
(2010/11/25)
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- 2′-Benzothiazolylthioesters of N-substituted alpha amino acids: Versatile intermediates for synthesis of ACE inhibitors
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ACE inhibitors have been synthesized from novel active esters using simple reaction conditions in high diastereomeric selectivity. The active esters may be obtained from the corresponding carboxylic acids or their acid chlorides.
- Singh, Girij Pal,Godbole, Himanshu M.,Nehate, Sagar P.,Mahajan, Pravin R.
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p. 243 - 248
(2007/10/03)
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- NOVEL METHOD FOR PREPARATION OF CRYSTALLINE PERINDOPRIL ERBUMINE
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A process for preparation of crystalline perindopril erbumine of formula (II) which exhibits the X-ray (powder) diffraction pattern like that shown in the figure. The process comprises reacting a solution of perindopril of formula (I), in a solvent selected from N, N-dimethylformamide or dimethyl acetals of lower aliphatic aldehydes and ketones with tertiary butylamine and crystallization of the erbumine salt thus obtained by heating the reaction mixture to reflux, filtering hot, cooling gradually to 20 oC to 30 oC, and further cooling to 0o C to 15 oC for 30 minutes to 1 hour and finally filtering off and drying the crystals.
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Page/Page column 51
(2010/02/11)
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- PROCESS FOR PURE PERINDOPRIL TERT-BUTYLAMINE SALT
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Pure perindopril tert-butylamine salt is obtained by extracting an aqueous solution of perindopril or its salt contaminated with impurities with a suitable organic solvent such as methylenedichloride at a pH of 4.0 to 6.5, separating the organic layer, isolating perindopril from the organic layer and converting it into tert-butylamine salt.
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Page/Page column 9
(2008/06/13)
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- PROCESS AND PRODUCT
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A process of preparing perindopril of formula (I), or a pharmaceutically acceptable salt thereof which process comprises protecting a compound of formula (II) where R denotes a hydrogen atom, in the presence of benzene sulphonic acid as a catalyst, to obtain the benzene sulphonic acid salt of an ester of formula (III) where Rl is a carboxyl protecting group and reacting said ester of formula (III) with N-[(S)-1-carbethoxybutyl]-(S)-alanine to obtain a compound of formula (IV) where Rl is as defined above; and deprotecting a compound of formula (IV) to yield perindopril of formula (I), or a pharmaceutically acceptable salt thereof. There is also provided by the present invention the benzene sulphonic acid salt of an ester of formula (III), and perindopril or a pharmaceutically acceptable salt thereof prepared by the above process.
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- A PROCESS FOR THE PREPARATION OF COMPOUNDS HAVING AN ACE INHIBITORY ACTION
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The present invention relates to the process for the preparation of compounds of formula (I) having an ACE inhibitory action wherein carboxy group of stereospecific amino acid is activated with an uronium salt in in the presence of an aprotic solvent and an activated amino acid is further transformed with appropriate amine into ACE inhibitor or its precursor.
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