WO2011051975A1 - An improved process for the preparation of pure eprosartanand its pharmaceutical acceptable salts - Google Patents
An improved process for the preparation of pure eprosartanand its pharmaceutical acceptable salts Download PDFInfo
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- WO2011051975A1 WO2011051975A1 PCT/IN2010/000709 IN2010000709W WO2011051975A1 WO 2011051975 A1 WO2011051975 A1 WO 2011051975A1 IN 2010000709 W IN2010000709 W IN 2010000709W WO 2011051975 A1 WO2011051975 A1 WO 2011051975A1
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- eprosartan
- hydrochloride
- pure
- crystalline form
- preparation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Definitions
- the present invention relates to an improved process for preparation of pure Eprosartan and its pharmaceutical acceptable salts.
- Eprosartan is a potent and selective angiotensin II subtype 1 receptor antagonist.
- Angiotensin II formed from Angiotensin I in a reaction catalyzed by Angiotensin - converting enzyme kininase II), a potent vasoconstrictor, is the principal pressor agent of the rennin-angiotension system.
- Angiotensin II also stimulates aldosterone synthesis and secretion by the adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth.
- Eprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the ATi receptor found in many tissues. By inhibiting the binding, Eprosartan disrupts the vasoconstriction mediated by ATI receptors and thus helps patients with hypertension.
- the chemical name for Eprosartan Mesylate is (E)-2 -butyl- l-(p-carboxybenzy l)-a-
- Eprosartan is prepared by reacting 4-[[2-butyl-5- formyl-lH-imidazol-l-yl]methyl]benzoic acid or the bisulfite addition compound of 4-[[2- butyl-5-formyl-l H-imidazol-l -yl]methyl]benzoic acid with (2-thienylmethyl)- propanedioic acid, mono-ethyl ester in a solvent (and/or solvent systems) selected from the group consisting of toluene, cyclohexane, cyclohexane:dichloroethane (12:5 or 1 : 1), cyclohexane:pyridine (12:5), and cyclohexane:ethyl acetate: pyridine (8:3: 1) in the presence of piperidine as catalyst at reflux temperature at reduced pressure followed by hydrolysis of the intermediate ethyl ester (ethyl (a)
- Eprosartan is prepared by reacting methyl-4-[[2-butyl-5- formyl-lH-imidazol-l-yl]methyl]benzoate with (2-thienylmethyl)-propanedioic acid, monoethyl ester in a solvent selected from cylcohexane and n-hexane in the presence of piperidine as catalyst at reflux temperature followed by hydrolysis.
- Eprosartan and its pharmaceutical acceptable salts is prepared by suspending Eprosartan acetate in water and adjusting the pH of the suspension with a base and collecting the substantially pure Eprosartan base, which further treated with Methane sulphonic acid to get Eprosartan Mesylate.
- Eprosartan obtained by the prior art process required the repeated crystallization in different solvents to get the desired quality of the Eprosartan.
- Eprosartan is isolated as Eprosartan hydrochloride by simple process and further converted into pharmaceutically acceptable salts with improved yield and quality.
- the main object of the present invention is to provide an improved process for the preparation of pure Eprosartan and its further conversion to Eprosartan Mesylate salt.
- Another object of the present invention is to provide pure Eprosartan hydrochloride.
- the present invention provides a process for the preparation, of Eprosartan Hydrochloride and its further conversion to Eprosartan Mesylate.
- the present invention provides a process for the preparation of Eprosartan Mesylate from pure Eprosartan. Brief description of the drawings
- Figure 1 shows the X-ray diffraction pattern of pure Eprosartan Hydrochloride obtained as per the present invention.
- Figure 2 shows the Diffrential Scanning Calorimetry pattern of pure Eprosartan Hydrochloride obtained as per the present invention.
- Figure 3 shows the Thermo gravimetric analysis pattern of pure Eprosartan Hydrochloride 10 obtained as per the present invention.
- the present invention relates to an improved process for the preparation of pure Eprosartan 15 and its further conversion to acid addition salts, wherein Eprosartan is reacted with HC1 to give Eprosartan Hydrochloride, which is suspended in water and then adjusted the resulted solution pH to give pure Eprosartan, which is further converted to its pharmaceutically acceptable salts by conventional method.
- the present invention provides a process for the preparation of Eprosartan hydrochloride comprising the steps of,
- Eprosartan is dissolved in DM water and Con HC1, heated to 70 - 100 °C, preferably 85-90 °C for 10-60 min, preferably 15-30 min. Then reaction mixture is cooled to 15- 40°C preferably 20- 30°C. The obtained solid was filtered to get Eprosartan hydrochloride.
- Eprosartan Hydrochloride is characterized by powder X-ray diffraction pattern as shown in Figure 1 with peaks at 8.26, 17.48, 19.07, 22.31 , 23.39, 24.64, 28.83 and 33.54 ⁇ 2 ⁇ values
- crystalline Eprosartan 5 Hydrochloride is characterized by powder X-ray diffraction pattern as shown in Figure 1. According to another embodiment of the present invention, crystalline Eprosartan Hydrochloride is further characterized by DSC as shown in Figures 2.
- crystalline Eprosartan Hydrochloride is further characterized by TGA as shown in Figures 3.
- the present invention provides a process for the purification of Eprosartan comprising the steps of,
- starting Eprosartan is prepared by the prior art processes described in US 6, 172,237, WO 2008/078330, WO 2009/013760, WO 2009/084028 and WO 2010/023688.
- the pH of the Eprosartan Hydrochloride suspension is adjusted by using an inorganic base selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, calcium bicarbonate, potassium bicarbonate or ammonium bicarbonate, preferably sodium hydroxide.
- an inorganic base selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, calcium bicarbonate, potassium bicarbonate or ammonium bicarbonate, preferably sodium hydroxide.
- pure Eprosartan is isolated by treating starting Eprosartan with hydrochloric acid and suspending the resulted Eprosartan hydrochloride in water and adjusting the pH of the suspension to 10-12 by using sodium or potassium hydroxide. Clear solution thus obtained is subjected to carbon treatment.
- the pH of the resulting filtrate is adjusted to 4-7 using appropriate acid such as hydrochloric acid to obtain pure Eprosartan.
- Eprosartan is isolated from Eprosartan hydrochloride by suspending Eprosartan hydrochloride in DM water, adjusting pH to 6.5-7.5 preferably 6.5-7 and isolating pure Eprosartan.
- Acid addition salts of Eprosartan are formed with the appropriate inorganic or organic acids by methods known in the art. Representative examples of suitable acids are maleic, fumaric, acetic, succinic, hydrochloric, hydrobromic, sulfuric, phosphoric or methanesulfonic.
- the pharmaceutically acceptable acid addition salt is methanesulfonic acid.
- the present invention also provides process for the conversion of pure Eprosartan to its acid addition salts preferably Eprosartan Mesylate by treating pure Eprosartan with methane sulfonic acid in the presence of acetic acid and a solvent selected from protic solvents such as isopropyl alcohol, methanol; ketone solvents such as methyl ethyl ketone, acetone and the like and ester solvents such as ethyl acetate, isopropyl acetate and the like.
- the resulted Eprosartan Mesylate is optionally purified in the presence of a solvent as described above and acetic acid to obtain pure Eprosartan Mesylate.
- the said polymorphs of the present invention are characterized by their X-ray powder diffraction pattern.
- the X-ray diffraction patterns of said polymorphs of the invention were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of ⁇ / ⁇ configuration and X'Celerator detector.
- the Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 20 range of 2.0°- 50.0°, 0.030° step size and 50 seconds step time.
- the DSC measurements were carried out on Mettler Toledo 822 star e and TA Q1000 of TA instruments. The experiments were performed at a heating rate of 10.0 °C/min over a temperature range of 30°C-300°C purging with nitrogen at a flow rate of 50ml/min. Standard aluminum crucibles covered by lids with three pin holes were used. Thermo gravimetric Analysis (TGA)
- TGA was recorded on out using the instrument Mettler Toledo TGA/SDTA 85 l e and TGA Q5000 of TA instruments. The experiments were performed at a heating rate of 10.0 °C/min over a temperature range of 30°C-300°C purging with nitrogen at a flow rate of 25ml/min.
- Eprosartan (10 g) was dissolved in DM water (50 mL) and Con. HC1 (8 mL) was added. The resulting solution was heated to 85-90°C with stirring and maintained for 15-30 minutes. The reaction mixture was cooled to 25°C over a period of one hour and maintained for 1-2 hours. The separated solid was filtered and washed with DM water and dried to get Eprosartan Hydrochloride.
- Eprosartan Hydrochloride in example 1 was suspended in water (50 mL) and the pH was adjusted to 6.5-7.0 by using 10% aqueous sodium hydroxide. Filtered the reaction mixture and washed with DM water and dried to get 9 gms of Pure Eprosartan.
- Eprosartan Hydrochloride in example 1 was suspended in water (50 mL) and the pH was adjusted to 1 1.5-12.0 by using 10% aqueous sodium hydroxide.
- activated carbon 1.0 gm
- the pH of the filtrate was adjusted to 4.5-5.0 by using hydrochloric acid and maintained for 2 hours. Filtered the reaction mixture and washed with DM water and dried to get 9 gms of Pure Eprosartan.
- Example 3 Preparation of Pure Eprosartan Mesylate
Abstract
The present invention relates to an improved process for preparation of pure Eprosartan and its pharmaceutical acceptable salts comprising the steps of: a) treating the Eprosartan with hydrochloric acid; b) suspending the resulted Eprosartan hydrochloride in water; c) adjusting the pH with base; d) isolating the pure Eprosartan; wherein the purity of the purified Eprosartan is higher than the purity of the starting Eprosartan.
Description
AN IMPROVED PROCESS FOR THE PREPARATION OF PURE
EPROSARTAN AND ITS PHARMACEUTICAL ACCEPTABLE SALTS
This application claims priority to Indian patent application No. 2638/CHE/2009 filed on October 30, 2009 the contents of which are incorporated by reference in their entirety.
Field of the Invention
The present invention relates to an improved process for preparation of pure Eprosartan and its pharmaceutical acceptable salts.
Background of the Invention
Eprosartan is a potent and selective angiotensin II subtype 1 receptor antagonist. Angiotensin II (formed from Angiotensin I in a reaction catalyzed by Angiotensin - converting enzyme kininase II), a potent vasoconstrictor, is the principal pressor agent of the rennin-angiotension system. Angiotensin II also stimulates aldosterone synthesis and secretion by the adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth. Eprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the ATi receptor found in many tissues. By inhibiting the binding, Eprosartan disrupts the vasoconstriction mediated by ATI receptors and thus helps patients with hypertension. The chemical name for Eprosartan Mesylate is (E)-2 -butyl- l-(p-carboxybenzy l)-a-
(2-thienylmethyl)imidazole-5-acrylic acid, monomethanesulfonate having the following structure of formula I.
Formula I
Processes for the preparations of Eprosartan and related compounds were disclosed in U.S. Patent No. 5,185,351, 6, 172,237 and PCT publication No. WO2008/078330.
According to the U.S. Patent No. 5, 185,351, methyl 4-[[2-butyl-5-formyl-lH-imidazol-l - yl]methyl]benzoate is reacted with ethyl 2-carboxy-3-(2-thienyl)propionate, in the presence of a base, such as piperidine, in a suitable solvent, like toluene, at a temperature of 80°C to 1 10°C, preferably at 100°C, to give ethyl (aE)-a-[[2-n-Butyl-l -[[4- (methoxycarbonyl)phenyl]methyl]-lH-imidazol-5-yl]methylene-2-thiophene propionate, which is then hydrolyzed to give Eprosartan, which is further converted to Eprosartan Mesylate.
According to U.S. Patent No. 6, 172,237, Eprosartan is prepared by reacting 4-[[2-butyl-5- formyl-lH-imidazol-l-yl]methyl]benzoic acid or the bisulfite addition compound of 4-[[2- butyl-5-formyl-l H-imidazol-l -yl]methyl]benzoic acid with (2-thienylmethyl)- propanedioic acid, mono-ethyl ester in a solvent (and/or solvent systems) selected from the group consisting of toluene, cyclohexane, cyclohexane:dichloroethane (12:5 or 1 : 1), cyclohexane:pyridine (12:5), and cyclohexane:ethyl acetate: pyridine (8:3: 1) in the presence of piperidine as catalyst at reflux temperature at reduced pressure followed by hydrolysis of the intermediate ethyl ester (ethyl (a£)-a-[[2-n-butyl-l -[[4- (methoxycarbonyl) phenyl]methyl]-l H-imidazol-5-yl]methylene-2-thiophene propionate). It is difficult to maintain the reaction at reflux under vacuum. The vacuum creates loss of solvent from reaction medium.
According to WO2008/078330, Eprosartan is prepared by reacting methyl-4-[[2-butyl-5- formyl-lH-imidazol-l-yl]methyl]benzoate with (2-thienylmethyl)-propanedioic acid, monoethyl ester in a solvent selected from cylcohexane and n-hexane in the presence of piperidine as catalyst at reflux temperature followed by hydrolysis.
According to WO2009/013760, Eprosartan and its pharmaceutical acceptable salts is prepared by suspending Eprosartan acetate in water and adjusting the pH of the suspension with a base and collecting the substantially pure Eprosartan base, which further treated with Methane sulphonic acid to get Eprosartan Mesylate.
Eprosartan obtained by the prior art process required the repeated crystallization in different solvents to get the desired quality of the Eprosartan.
Therefore there is a need for an improved and commercially viable process of preparing pure Eprosartan, which will be suitable for large-scale preparation, in terms of chemical yield and purity of the product.
According to the present invention Eprosartan is isolated as Eprosartan hydrochloride by simple process and further converted into pharmaceutically acceptable salts with improved yield and quality.
Obj ect of the Invention
The main object of the present invention is to provide an improved process for the preparation of pure Eprosartan and its further conversion to Eprosartan Mesylate salt.
Another object of the present invention is to provide pure Eprosartan hydrochloride.
Summary of the Invention
In accordance with one aspect of the present invention, there is provided a process for the purification of Eprosartan comprising the steps of,
a) treating the Eprosartan with hydrochloric acid,
b) suspending the resulted Eprosartan hydrochloride in water,
c) adjusting the pH of the suspension with base and
d) isolating the purified Eprosartan .
In another aspect, the present invention provides a process for the preparation, of Eprosartan Hydrochloride and its further conversion to Eprosartan Mesylate.
In another aspect, the present invention provides a process for the preparation of Eprosartan Mesylate from pure Eprosartan.
Brief description of the drawings
Figure 1 shows the X-ray diffraction pattern of pure Eprosartan Hydrochloride obtained as per the present invention.
■ 5
Figure 2 shows the Diffrential Scanning Calorimetry pattern of pure Eprosartan Hydrochloride obtained as per the present invention.
Figure 3 shows the Thermo gravimetric analysis pattern of pure Eprosartan Hydrochloride 10 obtained as per the present invention.
Detailed description of the Invention
The present invention relates to an improved process for the preparation of pure Eprosartan 15 and its further conversion to acid addition salts, wherein Eprosartan is reacted with HC1 to give Eprosartan Hydrochloride, which is suspended in water and then adjusted the resulted solution pH to give pure Eprosartan, which is further converted to its pharmaceutically acceptable salts by conventional method.
20 Accordingly the present invention provides a process for the preparation of Eprosartan hydrochloride comprising the steps of,
a) treating the Eprosartan with hydrochloric acid; and
b) isolating Eprosartan hydrochloride. 5 According to the present invention one embodiment of the present invention, Eprosartan is dissolved in DM water and Con HC1, heated to 70 - 100 °C, preferably 85-90 °C for 10-60 min, preferably 15-30 min. Then reaction mixture is cooled to 15- 40°C preferably 20- 30°C. The obtained solid was filtered to get Eprosartan hydrochloride.
30 According to another embodiment of the present invention, Eprosartan Hydrochloride is characterized by powder X-ray diffraction pattern as shown in Figure 1 with peaks at 8.26, 17.48, 19.07, 22.31 , 23.39, 24.64, 28.83 and 33.54 ± 2Θ values
According to another embodiment of the present invention, crystalline Eprosartan 5 Hydrochloride is characterized by powder X-ray diffraction pattern as shown in Figure 1.
According to another embodiment of the present invention, crystalline Eprosartan Hydrochloride is further characterized by DSC as shown in Figures 2.
According to another embodiment of the present invention, crystalline Eprosartan Hydrochloride is further characterized by TGA as shown in Figures 3.
The present invention provides a process for the purification of Eprosartan comprising the steps of,
c) treating the Eprosartan with hydrochloric acid;
d) suspending the resulted Eprosartan hydrochloride in water ;
e) adjusting the pH of the suspension with base;
f) isolating the purified Eprosartan ;
wherein the purity of the purified Eprosartan is higher than the purity of the starting Eprosartan. According to one embodiment of the present invention starting Eprosartan is prepared by the prior art processes described in US 6, 172,237, WO 2008/078330, WO 2009/013760, WO 2009/084028 and WO 2010/023688.
According to another embodiment of the present invention, the pH of the Eprosartan Hydrochloride suspension is adjusted by using an inorganic base selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, calcium bicarbonate, potassium bicarbonate or ammonium bicarbonate, preferably sodium hydroxide. According to the present invention pure Eprosartan is isolated by treating starting Eprosartan with hydrochloric acid and suspending the resulted Eprosartan hydrochloride in water and adjusting the pH of the suspension to 10-12 by using sodium or potassium hydroxide. Clear solution thus obtained is subjected to carbon treatment. The pH of the resulting filtrate is adjusted to 4-7 using appropriate acid such as hydrochloric acid to obtain pure Eprosartan.
Alternatively pure Eprosartan is isolated from Eprosartan hydrochloride by suspending Eprosartan hydrochloride in DM water, adjusting pH to 6.5-7.5 preferably 6.5-7 and isolating pure Eprosartan. Acid addition salts of Eprosartan are formed with the appropriate inorganic or organic acids by methods known in the art. Representative examples of suitable acids are maleic, fumaric, acetic, succinic, hydrochloric, hydrobromic, sulfuric, phosphoric or methanesulfonic. Preferably, the pharmaceutically acceptable acid addition salt is methanesulfonic acid. The present invention also provides process for the conversion of pure Eprosartan to its acid addition salts preferably Eprosartan Mesylate by treating pure Eprosartan with methane sulfonic acid in the presence of acetic acid and a solvent selected from protic solvents such as isopropyl alcohol, methanol; ketone solvents such as methyl ethyl ketone, acetone and the like and ester solvents such as ethyl acetate, isopropyl acetate and the like. The resulted Eprosartan Mesylate is optionally purified in the presence of a solvent as described above and acetic acid to obtain pure Eprosartan Mesylate.
Instrumentation:
Powder X-ray Diffraction (PXRD)
The said polymorphs of the present invention are characterized by their X-ray powder diffraction pattern. Thus, the X-ray diffraction patterns of said polymorphs of the invention were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of Θ/Θ configuration and X'Celerator detector. The Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 20 range of 2.0°- 50.0°, 0.030° step size and 50 seconds step time.
Differential Scanning Calorimetry (DSC)
The DSC measurements were carried out on Mettler Toledo 822 stare and TA Q1000 of TA instruments. The experiments were performed at a heating rate of 10.0 °C/min over a temperature range of 30°C-300°C purging with nitrogen at a flow rate of 50ml/min. Standard aluminum crucibles covered by lids with three pin holes were used.
Thermo gravimetric Analysis (TGA)
TGA was recorded on out using the instrument Mettler Toledo TGA/SDTA 85 le and TGA Q5000 of TA instruments. The experiments were performed at a heating rate of 10.0 °C/min over a temperature range of 30°C-300°C purging with nitrogen at a flow rate of 25ml/min.
The following examples are given for the purpose of illustrating the present invention and should not be considered as limitation on the scope or spirit of the invention. Examples
Example 1 : Preparation of Eprosartan Hydrochloride
Eprosartan (10 g) was dissolved in DM water (50 mL) and Con. HC1 (8 mL) was added. The resulting solution was heated to 85-90°C with stirring and maintained for 15-30 minutes. The reaction mixture was cooled to 25°C over a period of one hour and maintained for 1-2 hours. The separated solid was filtered and washed with DM water and dried to get Eprosartan Hydrochloride.
Example 2: Process for the preparation of Pure Eprosartan
Method A
The obtained Eprosartan Hydrochloride in example 1 was suspended in water (50 mL) and the pH was adjusted to 6.5-7.0 by using 10% aqueous sodium hydroxide. Filtered the reaction mixture and washed with DM water and dried to get 9 gms of Pure Eprosartan. Method B
The obtained Eprosartan Hydrochloride in example 1 was suspended in water (50 mL) and the pH was adjusted to 1 1.5-12.0 by using 10% aqueous sodium hydroxide. To the obtained reaction mixture activated carbon (1.0 gm) was added. Stirred the reaction mass filtered through hyflo bed and washed with water. The pH of the filtrate was adjusted to 4.5-5.0 by using hydrochloric acid and maintained for 2 hours. Filtered the reaction mixture and washed with DM water and dried to get 9 gms of Pure Eprosartan.
Example 3: Preparation of Pure Eprosartan Mesylate
Pure Eprosartan (10 g) obtained in Example 2 was added to ethyl acetate (30 mL) at room temperature and methane sulfonic acid (2.8 g) was added. The reaction mass was stirred for 1 -2 hours and acetic acid (70 mL) was added. The resulted reaction mass was heated to 75-80°C and maintained for about 15- 30 minutes. To the resulted solution activated carbon (1 g) was added and maintained for about 30 minutes. Filtered the solid through hyflow bed (0.5 g) and washed with hot acetic acid (10 mL) at 50-60°C. Cooled the reaction mass to 30°C and washed with ethyl acetate (70 mL) and dried the solid under vacuum to get pure Eprosartan Mesylate (10 g).
Claims
1. An improved process for the purification of Eprosartan comprising the steps of; a) treating the Eprosartan with hydrochloric acid;
b) suspending the resulted Eprosartan hydrochloride in water ;
c) adjusting the pH with base;
d) isolating the pure Eprosartan ;
wherein the purity of the purified Eprosartan is higher than the purity of the starting Eprosartan.
2. The process according o the claim 1, wherein the base used in step-c is an inorganic base selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, calcium bicarbonate, potassium bicarbonate or ammonium bicarbonate.
3. The process according to the claim 1, where the pH in step-c is adjusted to 6.5-7.5 to isolate pure Eprosartan.
4. The process according to the claim 1, where the pH in step-c is adjusted to basic; optionally treating with carbon; adjusting the pH to 4-7 with an acid; to isolate pure Eprosartan.
5. The process according to the claims 1 -4, wherein the eporsartan is further converted into acid addition salts.
6. The process according to the claims 5, wherein the acid addition salt is mesylate.
7. A process for the preparation of Eprosartan hydrochloride comprising the steps of, a) treating the Eprosartan with hydrochloric acid; and
b) isolating Eprosartan hydrochloride.
8. A crystalline form of Eprosartan Hydrochloride characterized by a powder X-ray diffraction pattern having peaks at about 8.26, 17.48, 19.07, 22.31, 23.39, 24.64, . 28.83 and 33.54 ± 2 Θ values.
9. A crystalline form of Eprosartan Hydrochloride according to claim 8, wherein the crystalline form is characterized by PXRD as depicted in Figure 1.
10. A crystalline form of Eprosartan Hydrochloride according to claim 8, wherein the crystalline form is characterized by DSC as depicted in figure 2.
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US5185351A (en) | 1989-06-14 | 1993-02-09 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists |
US6172237B1 (en) | 1997-02-14 | 2001-01-09 | Smithkline Beecham Corporation | Process for preparing eprosartan |
US20060099230A1 (en) * | 2004-11-10 | 2006-05-11 | Chin-Chih Chiang | Novel formulations of eprosartan with enhanced bioavailability |
WO2008078330A1 (en) | 2006-12-27 | 2008-07-03 | Hetero Drugs Limited | Improved process for eprosartan |
WO2009013760A2 (en) | 2007-07-25 | 2009-01-29 | Hetero Drugs Limited | Eprosartan mesylate crystalline particles and a process for preparing pure eprosartan |
WO2009084028A2 (en) | 2007-12-03 | 2009-07-09 | Neuland Laboratories Ltd | Improved process for manufacturing anhydrous (e)-3-[2-butyl-1- {(4-carboxyphenyl) methyl}-1h-imidazole-5-yl]-(thiophen-2- ylmethyl)prop-2-enoic acid methane sulfonate |
WO2010023688A2 (en) | 2008-08-25 | 2010-03-04 | Matrix Laboratories Limited | An improved process for the preparation of eprosartan |
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2010
- 2010-10-29 WO PCT/IN2010/000709 patent/WO2011051975A1/en active Application Filing
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US5185351A (en) | 1989-06-14 | 1993-02-09 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists |
US6172237B1 (en) | 1997-02-14 | 2001-01-09 | Smithkline Beecham Corporation | Process for preparing eprosartan |
US20060099230A1 (en) * | 2004-11-10 | 2006-05-11 | Chin-Chih Chiang | Novel formulations of eprosartan with enhanced bioavailability |
WO2008078330A1 (en) | 2006-12-27 | 2008-07-03 | Hetero Drugs Limited | Improved process for eprosartan |
WO2009013760A2 (en) | 2007-07-25 | 2009-01-29 | Hetero Drugs Limited | Eprosartan mesylate crystalline particles and a process for preparing pure eprosartan |
WO2009084028A2 (en) | 2007-12-03 | 2009-07-09 | Neuland Laboratories Ltd | Improved process for manufacturing anhydrous (e)-3-[2-butyl-1- {(4-carboxyphenyl) methyl}-1h-imidazole-5-yl]-(thiophen-2- ylmethyl)prop-2-enoic acid methane sulfonate |
WO2010023688A2 (en) | 2008-08-25 | 2010-03-04 | Matrix Laboratories Limited | An improved process for the preparation of eprosartan |
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DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 19 March 2010 (2010-03-19), SAMPATHKUMAR, UPPARAPALLI ET AL: "A method for the preparation of Eprosartan", XP002618304, retrieved from STN Database accession no. 2010:397062 * |
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