WO2005019173A1 - Process for pure perindopril tert-butylamine salt - Google Patents
Process for pure perindopril tert-butylamine salt Download PDFInfo
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- WO2005019173A1 WO2005019173A1 PCT/IN2003/000276 IN0300276W WO2005019173A1 WO 2005019173 A1 WO2005019173 A1 WO 2005019173A1 IN 0300276 W IN0300276 W IN 0300276W WO 2005019173 A1 WO2005019173 A1 WO 2005019173A1
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- perindopril
- butylamine
- tert
- salt
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- QJOOVIKYGHHVEX-IGTVTNBPSA-N CCCC(C(N1C2CCCCC2)=O)N([C@@H](C)C(N(C(C2)C(O)=O)[C@@H]3[C@H]2CCCC3)=O)/C1=N/C1CCCCC1 Chemical compound CCCC(C(N1C2CCCCC2)=O)N([C@@H](C)C(N(C(C2)C(O)=O)[C@@H]3[C@H]2CCCC3)=O)/C1=N/C1CCCCC1 QJOOVIKYGHHVEX-IGTVTNBPSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Definitions
- the present invention relates to a process for obtaining pure perindopril tert-butylamine salt.
- (2S,3aS,7aS)-1-[(2S)-2-[[(1 S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl] octahydro-1H-indole-2-carboxylic acid and its tert-butylamine salt are angiotensin-converting enzyme inhibitors.
- the therapeutic uses of perindopril and related compounds and their preparations are disclosed in US 4,508,729 and US 4,914,214.
- US 4,914,214 describes an industrial process for preparation of perindopril and perindopril tert-butylamine salt. According to US 4,914,214 benzyl ester of formula
- WO 0158868 describes a process for preparation of perindopril and perindopril tert-butylamine salt. According to WO 0158868 toluenesulfonate of compound of formula
- perindopril benzyl ester which is hydrogenated and converted into perindopril tert-butylamine salt.
- the process controls the formation of the impurities of formula VII and VIII. This process also suffers from drawbacks since the process requires strict control of quantities of reactants and is unable to remove other common impurities such as those of formula II to VI.
- impurities can be isolated from perindopril by extracting an aqueous solution of perindopril or its salt contaminated with impurities with a suitable organic solvent under suitable conditions. The impurities remain in the aqueous phase and perindopril extracted into the organic phase is then converted to pure perindopril tert-butylamine salt.
- the novel method provides a simple and economical process for obtaining pure perindopril tert-butylamine salt and since perindopril tert-butylamine salt obtained is with high purity, the product can be used in pharmaceutical preparations.
- SUMMARY OF THE INVENTION The present invention provides a simple process for obtaining substantially pure perindopril tert-butylamine. Impurities that are commonly associated with perindopril are:
- a process for obtaining substantially pure perindopril tert-butylamine salt which comprises the steps of: a) extracting an aqueous solution of impure perindopril or an impure perindopril salt with an organic solvent selected from methylenedichloride, chloroform, ethylenedichloride, toluene, heptane and a mixture thereof at pH 4.0 to 6.5; b) separating and concentrating the organic layer obtained in step (a); c) dissolving the concentrate obtained in step (b) in a solvent selected from ethylacetate, methanol, ethanol, isopropyl alcohol, acetonitrile, dioxane and a mixture thereof; d) mixing tert-butylamine to the solution obtained in step (c ); and e) precipitating perindopril tert-butylamine salt from the solution obtained in step (d ).
- An aqueous solution of impure perindopril or a perindopril salt can be prepared, for example, by dissolving perindopril or a perindopril salt such as perindopril tert-butylamine salt contaminated with known or unknown impurities in water or water mixed with any other solvent.
- Perindopril or a salt thereof prepared in an aqueous media may also be used in step (a).
- the pH of the solution is adjusted to 4.0 to 6.5, preferably to 4.5 to 6.0 with an acid such as hydrochloric acid or sulfuric acid or a base such as sodium hydroxide, sodium or potassium carbonate, sodium or potassium bicarbonate or ammonia as required.
- aqueous solution of perindopril is extracted with a solvent selected from methylenedichloride, which is preferable, chloroform, ethylenedichloride, toluene, heptane and a mixture thereof.
- Precipitation in step (e) may be initiated by a method usually known in the art such as cooling, seeding, partial removal of the solvent from the solution or a combination thereof.
- "Impure perindopril (or impure perindopril salt)" refers throught out the specification to perindopril (or perindopril salt) with total impurity content (by weight) of about 3.0% or above.
- substantially pure perindopril tert-butylamine refers to perindopril tert- butylamine having chromatographic purity of not less than 97%, preferably not less than 99% and more preferably not less than 99.5%.
- Perindopril salts such as tert-butyl amine salt produced by the prior art methods are contaminated with known and/or unknown impurities in significant amounts. The commonest among the impurities are:
- Impure perindopril or an impure perindopril salt such as perindopril tert- butylamine salt is dissolved in water or water mixed with any other solvent.
- "Impure perindopril (or impure perindopril salt)" refers to perindopril (or perindopril salt) with total impurity content (by weight) of about 3.0% or above.
- An aqueous solution obtained' as a part of preparing perindopril or a salt thereof may also be used in the novel process for obtaining a substantially pure perindopril salt. The pH of the solution varies with the method of preparation, the salt used etc.
- the pH of the solution is then adjusted to 4.0 to 6.5, preferably to 4.5 to 6.0 with an acid such as hydrochloric acid or sulfuric acid or a base such as sodium hydroxide, sodium or potassium carbonate, sodium or potassium bicarbonate or ammonia as required.
- the aqueous solution after pH adjustment is extracted with an organic solvent selected from methylenedichloride, chloroform, ethylenedichloride, toluene, heptane and a mixture thereof.
- Perindopril is extracted into the organic phase and the impurities remain in the aqueous phase thereby effectively isolating perindopril from the impurities.
- the aqueous solution of perindopril is preferably extracted with methylenedichloride.
- the pH adjustment may also be done after mixing impure perindopril or its salt, the solvent for extraction and water.
- the phases are separated and the organic layer is concentrated by distilling off the solvent.
- the concentrate is dissolved in a solvent selected from ethylacetate, which is preferred, methanol, ethanol, isopropyl alcohol, acetonitrile, dioxane and a mixture thereof.
- the solution is optionally filtered.
- Tert-butylamine is added to the solution.
- the amount of tert-butylamine to perindopril present in the solution is not critical but at least one mole of tert- butylamine per mole of perindopril is preferably used for good yield.
- the contents may be heated.
- Substantially pure perindpril tert-butylamine salt is precipitated from the solution.
- the precipitation may be initiated by a commonly known method in the art such as cooling, seeding, partial removal of the solvent from the solution or a combination thereof.
- Some or whole of the steps of the process may be repeated for obtaining perindopril tert-butylamine with desired purity, but by suitable choice of the conditions and solvents a single run may be enough for obtaining substantially pure perindopril tert-butylamine.
- Substantially pure perindopril tert-butylamine refers to perindopril tert- butylamine having chromatographic purity of not less than 97%, preferably not less than 99% and more preferably not less than 99.5%.
- Example 1 Perindopril tert-butylamine salt ( 15 gm, purity: 92.4%) is added to water (100 ml) and methylenedichloride (100 ml) and the pH of the mass is adjusted to 5.4 by using 20% dilute hydrochloric acid. The phases are separated and the aqueous layer is washed with methylenedichloride (2 x 75 ml). The methylenedichloride layer and washings are combined and the combined organic phase is washed with water (50 ml) and then with 10% aq.sodium chloride (50 ml). The organic layer is dried over sodium sulphate and concentrated to give a residue (99.3% purity).
- Example 2 Ethylacetate (1800 ml) is added to (2S,3aS,7aS)- octahydro-1 H-indole-2- carboxylic acid benzyl ester (300 gm) at 25°C and stirred for 30 min. The reaction mass is cooled to 10°C, triethylamine (172.5 gm) is added and stirred for 5 minutes to form a clear solution. Hydroxybenzotriazole monohydrate (105 gm), dicyclohexylcarbodiimide (150 gm) are added to the reaction mass at 25°C under stirring.
- Example 3 The mixture of (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl) butyl]amino]-1-oxopropyl]octahydro-1H-indole-2-carboxylic acid benzyl ester (300 gm, obtained in example 2), cyclohexane (750 ml), water (1050 ml) and 5% palladium-charcoal (60 gm) is taken in a hydrogenation flask and subjected to hydrogenation under a hydrogen pressure of 2 bars for 10 hours. The reaction mass is filtered over hiflo and washed with DM water (200 ml).
- the layers are separated and the aqueous layer is washed with cyclohexane (900 ml) and the pH of the aqueous layer is adjusted to 5.7 by using aqueous ammonia. Then the aqueous layer is extracted with methylenedichloride (3000 ml), collected the organic layer and washed with water (500 ml).
- reaction mass is stirred for 4 hour at 25°C, cooled to 0°C to 5°C and stirred for 2 hours at the same temperature.
- the mass is filtered, washed the solid collected with ethyl acetate (100 ml) and dried at 50°C to give 180 gm of 99.8 % pure perindopril tert-butylamine salt.
- Example 3 is repeated except that after hydrogenation, layer separation and washing the aqueous layer with cyclohexane, (2S,3aS,7aS)-1-[(2S)-2- [[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-1 H-indole-2- carboxylic acid is collected by freeze-drying.
- Example 4 is repeated using the product thus obtained to give perindopril tert-butylamine with 95.5% purity.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Indole Compounds (AREA)
Abstract
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.
Description
PROCESS FOR PURE PERINDOPRIL tert- BUTYLAMINE SALT
FIELD OF THE INVENTION The present invention relates to a process for obtaining pure perindopril tert-butylamine salt. BACKGROUND OF THE INVENTION
Perindopril of formula I
Or (2S,3aS,7aS)-1-[(2S)-2-[[(1 S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl] octahydro-1H-indole-2-carboxylic acid and its tert-butylamine salt are angiotensin-converting enzyme inhibitors. The therapeutic uses of perindopril and related compounds and their preparations are disclosed in US 4,508,729 and US 4,914,214. US 4,914,214 describes an industrial process for preparation of perindopril and perindopril tert-butylamine salt. According to US 4,914,214 benzyl ester of formula
i COOCH2C6H5 
is condensed with the compound of formula
which is then subjected to hydrogenation in the presence of Pd/C to give perindopril, which is then dissolved in ethylacetate, tert-butylamine is added and finally crystallized to obtain perindopril tert-butylamine salt. The process described in US 4,914,214 is not satisfactory from purity point of view and there is a need for a process for obtaining pure perindopril tert- butylamine salt that can be used in pharmaceutical preparation. Impurities that are commonly associated with perindopril are:
WO 0158868 describes a process for preparation of perindopril and perindopril tert-butylamine salt. According to WO 0158868 toluenesulfonate of compound of formula
is condensed with the compound of formula
Impure perindopril or an impure perindopril salt such as perindopril tert- butylamine salt is dissolved in water or water mixed with any other solvent. "Impure perindopril (or impure perindopril salt)" refers to perindopril (or perindopril salt) with total impurity content (by weight) of about 3.0% or above. An aqueous solution obtained' as a part of preparing perindopril or a salt thereof may also be used in the novel process for obtaining a substantially pure perindopril salt. The pH of the solution varies with the method of preparation, the salt used etc. The pH of the solution is then adjusted to 4.0 to 6.5, preferably to 4.5 to 6.0 with an acid such as hydrochloric acid or sulfuric acid or a base such as sodium hydroxide, sodium or potassium carbonate, sodium or potassium bicarbonate or ammonia as required. The aqueous solution after pH adjustment is extracted with an organic solvent selected from methylenedichloride, chloroform, ethylenedichloride, toluene, heptane and a mixture thereof. Perindopril is extracted into the organic phase and the impurities remain in the aqueous phase thereby effectively isolating perindopril from the impurities. The aqueous solution of perindopril is preferably extracted with methylenedichloride.
The pH adjustment may also be done after mixing impure perindopril or its salt, the solvent for extraction and water. The phases are separated and the organic layer is concentrated by distilling off the solvent. The concentrate is dissolved in a solvent selected from ethylacetate, which is preferred, methanol, ethanol, isopropyl alcohol, acetonitrile, dioxane and a mixture thereof. The solution is optionally filtered. Tert-butylamine is added to the solution. The amount of tert-butylamine to perindopril present in the solution is not critical but at least one mole of tert- butylamine per mole of perindopril is preferably used for good yield. After the addition of tert-butylamine, If necessary, the contents may be heated. Substantially pure perindpril tert-butylamine salt is precipitated from the solution. The precipitation may be initiated by a commonly known method in the art such as cooling, seeding, partial removal of the solvent from the solution or a combination thereof. Some or whole of the steps of the process may be repeated for obtaining perindopril tert-butylamine with desired purity, but by suitable choice of the conditions and solvents a single run may be enough for obtaining substantially pure perindopril tert-butylamine. "Substantially pure" perindopril tert-butylamine refers to perindopril tert- butylamine having chromatographic purity of not less than 97%, preferably not less than 99% and more preferably not less than 99.5%. The invention will now be further described by the following example, which is illustrative rather than limiting.
Example 1 Perindopril tert-butylamine salt ( 15 gm, purity: 92.4%) is added to water (100 ml) and methylenedichloride (100 ml) and the pH of the mass is adjusted to 5.4 by using 20% dilute hydrochloric acid. The phases are separated and the aqueous layer is washed with methylenedichloride (2 x 75 ml). The methylenedichloride layer and washings are combined and the combined organic phase is washed with water (50 ml) and then with 10% aq.sodium
chloride (50 ml). The organic layer is dried over sodium sulphate and concentrated to give a residue (99.3% purity). Ethyl acetate (255 ml) is added to the residue (15 gm) and stirred for 10 min to obtain a clear solution. tert-Butyl amine is added drop wise to the solution at 30°C and stirred for 1 hour at the same temperature. The reaction mass is then heated to reflux, passed over hiflo rapidly at reflux temperature and washed with hot ethyl acetate (30 ml). Then the reaction mass is stirred for 2 hours at about 30°C, cooled to 0°C and stirred for further 2 hours at 0°C to 5°C. The separated solid is filtered, washed with ethylacetate (15 ml) and dried to give 12 gm of 99.77% pure perindopril tert-butylamine salt.
Example 2 Ethylacetate (1800 ml) is added to (2S,3aS,7aS)- octahydro-1 H-indole-2- carboxylic acid benzyl ester (300 gm) at 25°C and stirred for 30 min. The reaction mass is cooled to 10°C, triethylamine (172.5 gm) is added and stirred for 5 minutes to form a clear solution. Hydroxybenzotriazole monohydrate (105 gm), dicyclohexylcarbodiimide (150 gm) are added to the reaction mass at 25°C under stirring. Then N-[(S)-1-carbethoxybutyl]-(S)-alanine (150 gm) is added to the reaction mass and stirred for 5 hours . The contents are filtered, the filtrate is washed with water (700 ml), 5% sodium bicarbonate solution (700 ml), water
(700 ml) and finally with sodium chloride (700 ml). Organic layer is dried and concentrated under vacuum. The concentrate is taken in cyclohexane (500 ml), filtered the unwanted salts over hiflo and washed with cyclohexane (100 ml). The filtrate is concentrated under vacuum at 60°C to give 300 gm of (2S,3aS,7aS)-1-[(2S)-2- [[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-1H-indole-2- carboxylic acid benzyl ester. Example 3 The mixture of (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl) butyl]amino]-1-oxopropyl]octahydro-1H-indole-2-carboxylic acid benzyl ester (300 gm, obtained in example 2), cyclohexane (750 ml), water (1050 ml) and 5% palladium-charcoal (60 gm) is taken in a hydrogenation flask and subjected to hydrogenation under a hydrogen pressure of 2 bars for 10 hours. The reaction mass is filtered over hiflo and washed with DM water (200 ml). The layers are
separated and the aqueous layer is washed with cyclohexane (900 ml) and the pH of the aqueous layer is adjusted to 5.7 by using aqueous ammonia. Then the aqueous layer is extracted with methylenedichloride (3000 ml), collected the organic layer and washed with water (500 ml). The organic layer is dried over sodium sulphate and concentrated under vacuum at 50°C to give 225 gm of (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl] octahydro-1 H-indole-2-carboxylic acid. Example 4 (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxo propyl]octahydro-1H-indole-2-carboxylic acid (225 gm) (concentrate obtained in example 3) is dissolved in ethyl acetate (3800 ml), tert-butylamine (56 gm) is added drop wise at about 30°C for 30 minutes and stirred for 1 hour at the same temperature. Then the temperature of the reaction mass is raised to about 70°C to form a clear solution, passed over hiflo bed while hot and the filtrate is cooled to 25°C. The reaction mass is stirred for 4 hour at 25°C, cooled to 0°C to 5°C and stirred for 2 hours at the same temperature. The mass is filtered, washed the solid collected with ethyl acetate (100 ml) and dried at 50°C to give 180 gm of 99.8 % pure perindopril tert-butylamine salt. Comparative example 1 Example 3 is repeated except that after hydrogenation, layer separation and washing the aqueous layer with cyclohexane, (2S,3aS,7aS)-1-[(2S)-2- [[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-1 H-indole-2- carboxylic acid is collected by freeze-drying. Example 4 is repeated using the product thus obtained to give perindopril tert-butylamine with 95.5% purity.
Claims
We claim:
1 ) A process for obtaining substantially pure perindopril tert-butylamine, which comprises the steps of: a) extracting an aqueous solution of impure perindopril or an impure perindopril salt with an organic solvent selected from methylenedichloride, chloroform, ethylenedichloride, toluene, heptane and a mixture thereof at pH 4.0 to 6.5; b) separating and concentrating the organic layer obtained in step (a); c) dissolving the concentrate obtained in step (b) in a solvent selected from ethylacetate, methanol, ethanol, isopropyl alcohol, acetonitrile, dioxane and a mixture thereof; d) mixing tert-butylamine to the solution obtained in step (c ); and e) precipitating perindopril tert-butylamine salt from the solution obtained in step (d ); wherein "substantially pure perindopril tert-butylamine" refers to perindopril tert- butylamine having chromatographic purity of not less than 97%.
2) A process according to claim 1 , wherein chromatographic purity of perindopril tert-butylamine obtained is not less than 99%.
3) A process according to claim 1 , wherein chromatographic purity of perindopril tert-butylamine obtained is not less than 99.5%.
4) A process according to claim 1 , wherein the organic solvent in step (a) is methylenedichloride.
5) A process according to claim 1 , wherein the aqueous solution of impure perindopril or the impure perindopril salt is prepared by dissolving impure perindopril or an impure perindopril salt in water.
6) A process according to claim 5, wherein the perindopril salt is perindopril tert-butylamine salt.
7) A process according to claim 1 , wherein the pH of the solution in step (a) is adjusted to 4.5 to 6.0. 8) A process according to claim 1 , wherein the pH adjustment in step (a) is effected with an acid or a base. 9) A process according to claim 8, wherein the acid is hydrochloric acid or sulfuric acid.
10) A process according to claim 8, wherein the base is selected from sodium hydroxide, sodium or potassium carbonate, sodium or potassium bicarbonate or ammonia.
11) A process according to claim 9, wherein the acid is hydrochloric acid.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003263584A AU2003263584A1 (en) | 2003-08-21 | 2003-08-21 | Process for pure perindopril tert-butylamine salt |
| PCT/IN2003/000276 WO2005019173A1 (en) | 2003-08-21 | 2003-08-21 | Process for pure perindopril tert-butylamine salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2003/000276 WO2005019173A1 (en) | 2003-08-21 | 2003-08-21 | Process for pure perindopril tert-butylamine salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2005019173A1 true WO2005019173A1 (en) | 2005-03-03 |
Family
ID=34204119
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2003/000276 Ceased WO2005019173A1 (en) | 2003-08-21 | 2003-08-21 | Process for pure perindopril tert-butylamine salt |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2003263584A1 (en) |
| WO (1) | WO2005019173A1 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG125976A1 (en) * | 2005-03-11 | 2006-10-30 | Servier Lab | New gama crystalline form of perindopril tert-butylamine salt, a process for its preparation and pharmaceutical compositions containing it |
| SG125975A1 (en) * | 2005-03-11 | 2006-10-30 | Servier Lab | New alpha crystalline form of perindopril tert-butylamine salt, a process for its preparation and pharmaceutical compositions containing it |
| WO2007017087A1 (en) * | 2005-07-25 | 2007-02-15 | Lek Pharmaceuticals D.D. | Process for the preparation of crystalline perindopril |
| WO2007017893A3 (en) * | 2005-05-05 | 2007-05-10 | Arch Pharmalabs Ltd | Preparation of novel crystalline form of perindopril erbumine monohydrate |
| JP2008115127A (en) * | 2006-11-07 | 2008-05-22 | Permachem Asia Ltd | Method for producing perindopril precursor, method for producing perindopril, and method for producing and purifying perindopril erbumine |
| WO2008125134A1 (en) * | 2007-04-13 | 2008-10-23 | Helm Ag | Process for the preparation of perindopril-tert-butylamine adsorbates |
| US20150252001A1 (en) * | 2012-10-10 | 2015-09-10 | Piramal Enterprises Limited | Process for preparation of perindopril intermediate |
| CN112047999A (en) * | 2020-09-18 | 2020-12-08 | 天津力生制药股份有限公司 | Preparation method of gamma-crystal form arginine perindopril salt |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001083439A2 (en) * | 2000-07-06 | 2001-11-08 | Les Laboratoires Serviers | Novel $g(y) crystalline form of perindopril tert-butylamine salt, preparation method, and pharmaceutical compositions containing same. |
| EP1279665A2 (en) * | 2001-07-24 | 2003-01-29 | Adir | A process for the preparation of perindopril, its analogous compounds and salts thereof using 2,5-dioxo-oxazolidine intermediate compounds |
-
2003
- 2003-08-21 AU AU2003263584A patent/AU2003263584A1/en not_active Abandoned
- 2003-08-21 WO PCT/IN2003/000276 patent/WO2005019173A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001083439A2 (en) * | 2000-07-06 | 2001-11-08 | Les Laboratoires Serviers | Novel $g(y) crystalline form of perindopril tert-butylamine salt, preparation method, and pharmaceutical compositions containing same. |
| EP1279665A2 (en) * | 2001-07-24 | 2003-01-29 | Adir | A process for the preparation of perindopril, its analogous compounds and salts thereof using 2,5-dioxo-oxazolidine intermediate compounds |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG125976A1 (en) * | 2005-03-11 | 2006-10-30 | Servier Lab | New gama crystalline form of perindopril tert-butylamine salt, a process for its preparation and pharmaceutical compositions containing it |
| SG125975A1 (en) * | 2005-03-11 | 2006-10-30 | Servier Lab | New alpha crystalline form of perindopril tert-butylamine salt, a process for its preparation and pharmaceutical compositions containing it |
| WO2007017893A3 (en) * | 2005-05-05 | 2007-05-10 | Arch Pharmalabs Ltd | Preparation of novel crystalline form of perindopril erbumine monohydrate |
| WO2007017087A1 (en) * | 2005-07-25 | 2007-02-15 | Lek Pharmaceuticals D.D. | Process for the preparation of crystalline perindopril |
| JP2009502833A (en) * | 2005-07-25 | 2009-01-29 | レツク・フアーマシユーテイカルズ・デー・デー | Method for producing crystalline perindopril |
| EA013018B1 (en) * | 2005-07-25 | 2010-02-26 | Лек Фармасьютиклз Д. Д. | Process for the preparation of crystalline perindopril |
| US7923570B2 (en) | 2005-07-25 | 2011-04-12 | Lek Pharmaceuticals, D.D. | Process for the preparation of crystalline perindopril |
| JP2008115127A (en) * | 2006-11-07 | 2008-05-22 | Permachem Asia Ltd | Method for producing perindopril precursor, method for producing perindopril, and method for producing and purifying perindopril erbumine |
| WO2008125134A1 (en) * | 2007-04-13 | 2008-10-23 | Helm Ag | Process for the preparation of perindopril-tert-butylamine adsorbates |
| US20150252001A1 (en) * | 2012-10-10 | 2015-09-10 | Piramal Enterprises Limited | Process for preparation of perindopril intermediate |
| CN112047999A (en) * | 2020-09-18 | 2020-12-08 | 天津力生制药股份有限公司 | Preparation method of gamma-crystal form arginine perindopril salt |
| CN112047999B (en) * | 2020-09-18 | 2022-12-02 | 天津力生制药股份有限公司 | Preparation method of gamma-crystal form arginine perindopril salt |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003263584A1 (en) | 2005-03-10 |
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