WO2006073519A1 - Olmesartan medoxomil with reduced levels of impurities - Google Patents
Olmesartan medoxomil with reduced levels of impurities Download PDFInfo
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- WO2006073519A1 WO2006073519A1 PCT/US2005/031483 US2005031483W WO2006073519A1 WO 2006073519 A1 WO2006073519 A1 WO 2006073519A1 US 2005031483 W US2005031483 W US 2005031483W WO 2006073519 A1 WO2006073519 A1 WO 2006073519A1
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- WIPO (PCT)
- Prior art keywords
- olm
- olmesartan medoxomil
- mtt
- impurities
- eliminate
- Prior art date
Links
- 239000012535 impurity Substances 0.000 title claims abstract description 41
- UQGKUQLKSCSZGY-UHFFFAOYSA-N Olmesartan medoxomil Chemical compound C=1C=C(C=2C(=CC=CC=2)C2=NNN=N2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C UQGKUQLKSCSZGY-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 239000002051 C09CA08 - Olmesartan medoxomil Substances 0.000 title claims abstract description 33
- 229960001199 olmesartan medoxomil Drugs 0.000 title claims abstract description 33
- IJOPLMOXIPGJIJ-UHFFFAOYSA-N (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 5-(2-hydroxypropan-2-yl)-2-propyl-3-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate Chemical compound C=1C=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C IJOPLMOXIPGJIJ-UHFFFAOYSA-N 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 14
- VUTZFAOGDXUYEJ-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methylbenzene Chemical compound C1=CC(C)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 VUTZFAOGDXUYEJ-UHFFFAOYSA-N 0.000 claims description 10
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 239000000523 sample Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- LZTRCELOJRDYMQ-UHFFFAOYSA-N triphenylmethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1=CC=CC=C1 LZTRCELOJRDYMQ-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NKWCGTOZTHZDHB-UHFFFAOYSA-N 1h-imidazol-1-ium-4-carboxylate Chemical compound OC(=O)C1=CNC=N1 NKWCGTOZTHZDHB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- GAQUHNKHOZJBIJ-UHFFFAOYSA-N 5-(2-methoxypropan-2-yl)-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical group CCCC1=NC(C(C)(C)OC)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 GAQUHNKHOZJBIJ-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
- 229940055053 benicar Drugs 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Definitions
- the impurities OLM-Me, OLM-Cl, and OLM-eliminate have no known medicinal effect.
- the impurities at the trityl olmesartan medoxomil (MTT) stage — MTT-Me, MTT-Cl, and MTT eliminate — are not used for synthesizing olmesartan medoxomil. Structures for MTT-Me, MTT-Cl, and MTT are described below.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention provides the preparation of olmesartan medoxomil containing less than about 0.1% of one or more of the impurities OLM-Me, OLM -C1, and OLM-eliminate.
Description
OLMESARTAN MEDOXOMIL WITH REDUCED LEVELS OF IMPURITIES
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60/640,232 filed January 3, 2005.
FIELD OF INVENTION
The present invention relates to olmesartan medoxomil with reduced levels of impurities.
BACKGROUND OF THE INVENTION
The chemical name for olmesartan medoxomil is 4-(l -hydroxy- 1 -methylethyl)-2- propyl-l-[[2'-(lH-tetrazol-5-yl)[l,r-biphenyl]-4-yl]methyl]-lH-imidazole-5-carboxylic acid (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl ester (Merck Index 13th ed.).
The chemical structure of olmesartan medoxomil is:
The empirical formula is C29H3ON6O6.
The molecular weight is 558.58.
Olmesartan medoxomil is a prodrug that is hydrolyzed during absorption, and it is a selective AT1 subtype angiotensin II receptor antagonist. Olmesartan medoxomil is disclosed by U.S. Patent No. 5,616,599 to Yanagisawa et al. It is marketed as BENICAR® in film- coated tablets of 5 mg, 20 mg, and 40 mg for treatment of hypertension in a human.
The synthesis of olmesartan medoxomil (OLM-Mod) per se is illustrated as follows (see also Annu. Rep. Sankyo Res. Lab 2003, 55, 1-91):
But this route of synthesis produces several impurities.
There is a need for processes for preparing olmesartan medoxomil with reduced levels of impurities. BRIEF DESCRIPTION OF THE FIGURES
Figure 1 depicts a typical chromatogram of a trityl olmesartan medoxomil (MTT) sample.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a process for preparing olmesartan medoxomil containing less than about 0.1% area by HPLC of one or more of the following impurities: OLM-Me, OLM-Cl, and OLM-eliminate. This process includes the steps of: obtaining a sample of trityl olmesartan medoxomil (MTT); measuring the amount of one or more impurities selected from the group consisting of MTT-Me, MTT-Cl, and MTT-eliminate in the sample of trityl olmesartan medoxomil; selecting a sample of trityl olmesartan medoxomil in which the amount of one or more of the measured impurities is less than about 0.1%; and synthesizing olmesartan medoxomil from the selected trityl olmesartan
medoxomil sample. Preferably, the amount of each of the three impurities in the starting material and/or the final product is less than about 0.1%. More preferably, the combined amount of the three impurities is less than about 0.1%.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a process for preparing olmesartan medoxomil containing less than about 0.1% area by HPLC of one or more of the impurities OLM-Me, OLM-Cl and OLM-eliminate.
Impurity OLM-Me is 4-(l-methoxy-l-methylethyl)-2-propyl-l-[2'-(lH-tetrazole-5- yl)biphenyl-4-ylmethyl]imidazole-5-carboxylic acid 5-methyl-2-oxo-l,3-dioxol-4-ylmethyl ester.
Impurity OLM-Cl is 4-(l-hydroxy-l-methylethyl)-2-ρropyl-l-[2'-(lH-tetrazole-5- yl)biphenyl-4-ylmethyl]imidazole-5-carboxylic acid 5-chloromethyl-2-oxo-l,3-dioxol-4- ylmethyl ester.
Impurity OLM-eliminate is 4-(l-methylethylene)-2-propyl-l-[2'-(lH-tetrazole-5- yl)biphenyl-4-ylmethyl]imidazole-5-carboxylic acid 5-chloromethyl-2-oxo-l ,3-dioxol-4- ylmethyl ester.
The chemical structures of impurities OLM-Me, OLM-Cl, and OLM-eliminate are:
OLM-Me OLM-Cl OLM-Elirainate
The precursors of impurities OLM-Me and OLM-eliminate can form during the Grignard reaction, reaction step D in the synthesis route described previously. The formation of the precursors of impurities OLM-Me and OLM-eliminate is illustrated as follows:
The precursor of impurity OLM-Cl can form during reaction step K when the coupling reagent chloro-medoxomil (4-chloromethyl-2-oxo-l,3-dioxolene) contains some dichloromedoxomil (4,5-dichloro-dimethyl-2-oxo-l ,3-dioxolene):
The impurities OLM-Me, OLM-Cl, and OLM-eliminate have no known medicinal effect. The impurities at the trityl olmesartan medoxomil (MTT) stage — MTT-Me, MTT-Cl, and MTT eliminate — are not used for synthesizing olmesartan medoxomil. Structures for MTT-Me, MTT-Cl, and MTT are described below.
By selecting trityl olmesartan medoxomil with low levels of MTT-Me, MTT-Cl, and MTT eliminate, one can use the selected MTT to synthesize olmesartan medoxomil with low levels of impurities OLM-Me, OLM-Cl, and OLM-eliminate. In one embodiment, the present invention provides a process for preparing olmesartan medoxomil containing less than about 0.1% area by HPLC of one or more of the following impurities: OLM-Me, OLM-Cl5 and OLM-eliminate. This process includes the steps of: obtaining a sample of trityl olmesartan medoxomil (MTT); measuring the amount of one or more impurities selected from the group consisting of MTT-Me, MTT-Cl, and MTT- eliminate in the sample of trityl olmesartan medoxomil; selecting a sample of trityl olmesartan medoxomil in which the amount of one or more of the measured impurities is less than about 0.1%; and synthesizing olmesartan medoxomil from the selected trityl olmesartan
medoxomil sample. Preferably, the amount of each of the three impurities in the starting material and/or the final product is less than about 0.1%. More preferably, the combined amount of the three impurities is less than about 0.1%.
The chemical structures of MTT-Me, MTT-Cl, and MTT-eliminate are:
MTT-Me MTT-CI MTT-EIiminate
The amounts of MTT-Me, MTT-Cl, and MTT-eliminate are measured using HPLC. The amounts of OLM-Me, OLM-Cl and OLM-eliminate are also measured using HPLC. An exemplary impurity profile determination is described in Example 1.
One can use any method known in the art to synthesize olmesartan medoxomil from trityl olmesartan medoxomil, such as the process described in U.S. Patent No. 5,616,599. Olmesartan medoxomil can be synthesized from trityl olmesartan medoxomil by a method including the steps of: contacting trityl olmesartan medoxomil with an acid in a water miscible organic solvent, with or without water, to obtain a solution of olmesartan medoxomil and a precipitate of triphenyl carbinol; separating the precipitate of triphenyl carbinol from the solution of olmesartan medoxomil; and contacting the solution of olmesartan medoxomil with a base to obtain a precipitate of olmesartan medoxomil. Preferably, trityl olmesartan medoxomil is contacted with the acid in a water miscible organic solvent and water. Most preferably, a mixture of acetone and water is used.
EXAMPLES
Impurity profile determination of MTT (raw material of olmesartan medoxomil)
Column & packing Discovery HS Cl 8 50*4.6 mm, 3μ C.N 269250-U Eluent A: 0.025 M NaClO4 adjusted to pH=2.5 with HClO4 Eluent B: Acetonitrile
Gradient of Eluent: Time (min) Eluent A (%) Eluent B (%
0 70 30
10 60 40
20 40 60
35 40 60
Stop time: 35 min
Equilibration time: 5 min
Flow: 1.5 ml/min
Detector: 220 nm
Injection volume: 10 μl
Diluent Acetonitrile
Column temperature 250C
Autosampler temperature 5°C
Sample solution preparation
Weigh accurately about 15 mg of MTT sample into a 50 ml volumetric flask, dissolve, and dilute to volume with diluent.
Method
Inject sample solutions continuing the chromatogram up to the end of gradient. Determine the area of each impurity using suitable integrator.
Calculations
Any impurity in a sample is calculated as follows: area impurity in sample
% Impurity in sample = x100 ^ Areas of all peaks
RRT of the substances
The detection limit in the HPLC method is 0.01%.
Example 1 : Preparation of erode olmesartan medoxomil
A 250 round bottom flask was loaded with MTT (10 g), acetone/water (2/2 vol.), and 3 eq OfH2SO4. The mixture was stirred at 4O0C, and after 2-4 hrs, triphenyl carbinol (TPC) was precipitated by the addition of water and filtrated out. NaHCO3 was added to the filtrate and the mixture was cooled to room temperature and stirred for 1 hr. Crude olmesartan medoxomil was obtained as white crystals (90% yield).
Example 2: Preparation of olmesartan medoxomil crystals
A lL flask was charged with acetone (4% water). Crude olmesartan medoxomil (10 g) was added, and the mixture was heated to reflux (1 hr). After cooling to room temperature, water (10 vol) was added. The mixture was stirred (1 hr). Then the precipitate was filtered and dried at 45°C under 10 mm Hg (yield 90 %).
Having thus described the invention with reference to particular preferred embodiments and illustrative examples, those in the art can appreciate modifications to the invention as described and illustrated that do not depart from the spirit and scope of the invention as disclosed in the specification. The examples are set forth to aid in understanding the invention but are not intended to, and should not be construed to, limit its scope in any way. The examples do not include detailed descriptions of conventional methods.
Claims
1. A process for preparing olmesartan medoxomil containing less than about 0.1% of one or more of OLM-Me, OLM-Cl, and OLM-eliminate, comprising: a) obtaining a sample of trityl olmesartan medoxomil; b) measuring the amount of one or more impurities selected from the group consisting of MTT-Me, MTT-Cl, and MTT-eliminate in the sample of trityl olmesartan medoxomil; c) selecting a sample of trityl olmesartan medoxomil in which the amount of one or more of the measured impurities is less than about 0.1%; and d) synthesizing olmesartan medoxomil from the trityl olmesartan medoxomil selected in step c).
2. The process of claim 1, wherein the amount of each of the impurities MTT-Me, MTT-Cl, and MTT-eliminate in the selected sample of step c) is less than about 0.1%.
3. The process of claim 1, wherein the combined amount of the impurities MTT-Me, MTT- Cl, and MTT-eliminate in the selected sample of step c) is less than about 0.1%.
4. The process of claim 1, wherein the one or more impurities in step b) is measured by HPLC.
5. The process of claim 1, wherein the amount of each of the impurities OLM-Me, OLM-Cl, and OLM-eliminate in the olmesartan medoxomil synthesized in step d) is less than about 0.1%.
6. The process of claim 5, wherein the combined amount of the impurities OLM-Me, OLM- Cl, and OLM-eliminate in the olmesartan medoxomil synthesized in step d) is less than about 0.1%.
7. The process of claim 5, wherein the impurities OLM-Me, OLM-Cl, and OLM-eliminate in the olmesartan medoxomil synthesized in step d) are measured by HPLC.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020097019913A KR20090108739A (en) | 2005-01-03 | 2005-09-02 | Olmesartan medoxomil with reduced levels of impurities |
| JP2007502129A JP2007526342A (en) | 2005-01-03 | 2005-09-02 | Olmesartan medoxomil with low levels of impurities |
| EP05796113A EP1716139A1 (en) | 2005-01-03 | 2005-09-02 | Olmesartan medoxomil with reduced levels of impurities |
| CA002592160A CA2592160A1 (en) | 2005-01-03 | 2005-09-02 | Olmesartan medoxomil with reduced levels of impurities |
| IL183233A IL183233A0 (en) | 2005-01-03 | 2007-05-15 | Olmesartan medoxomil with reduced levels of impurities |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64023205P | 2005-01-03 | 2005-01-03 | |
| US60/640,232 | 2005-01-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2006073519A1 true WO2006073519A1 (en) | 2006-07-13 |
Family
ID=35462418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2005/031483 WO2006073519A1 (en) | 2005-01-03 | 2005-09-02 | Olmesartan medoxomil with reduced levels of impurities |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7563814B2 (en) |
| EP (1) | EP1716139A1 (en) |
| JP (1) | JP2007526342A (en) |
| KR (1) | KR20090108739A (en) |
| CN (1) | CN101094850A (en) |
| CA (1) | CA2592160A1 (en) |
| IL (1) | IL183233A0 (en) |
| WO (1) | WO2006073519A1 (en) |
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| WO2010126013A1 (en) | 2009-04-28 | 2010-11-04 | 第一三共株式会社 | Method for producing olmesartan medoxomil |
| WO2010126014A1 (en) | 2009-04-28 | 2010-11-04 | 第一三共株式会社 | Novel solvate crystals |
| AT509493B1 (en) * | 2006-09-15 | 2012-01-15 | Daiichi Sankyo Co Ltd | SOLID MEDICAMENT OF OLMESARTAN MEDOXOMIL AND AMLODIPIN |
| WO2012069025A1 (en) | 2010-11-24 | 2012-05-31 | Zentiva, K.S. | (5-methyl-2-oxo-1,3-dioxol-4-ylmethyl)-4-(1-hydroxy-1-methyl-propyl)-2-propyl-1-[2'- (1h-tetrazol-5-yl)biphenyl-4-yl-methyl]imidazole-5-carboxylate as an impurity of olmesartan medoxomil and a method of its preparation |
| WO2013021312A1 (en) * | 2011-08-05 | 2013-02-14 | Lupin Limited | Process for the preparation of olmesartan medoxomil |
| US8735598B2 (en) | 2008-06-09 | 2014-05-27 | Daiichi Sankyo Company, Limited | Method for producing 1-biphenylmethylimidazole compound |
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| GB0710680D0 (en) * | 2007-06-05 | 2007-07-11 | Generics Uk Ltd | Novel crystalline form of olmesartan medoxmil |
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| ITMI20032338A1 (en) | 2003-11-28 | 2005-05-29 | Dinamite Dipharma S P A In Forma A Bbreviata Diph | PHENYLTETRAZOLIC COMPOUNDS. |
-
2005
- 2005-09-02 CA CA002592160A patent/CA2592160A1/en not_active Abandoned
- 2005-09-02 EP EP05796113A patent/EP1716139A1/en not_active Withdrawn
- 2005-09-02 JP JP2007502129A patent/JP2007526342A/en active Pending
- 2005-09-02 US US11/217,473 patent/US7563814B2/en not_active Expired - Fee Related
- 2005-09-02 CN CNA2005800457872A patent/CN101094850A/en active Pending
- 2005-09-02 KR KR1020097019913A patent/KR20090108739A/en not_active Application Discontinuation
- 2005-09-02 WO PCT/US2005/031483 patent/WO2006073519A1/en active Application Filing
-
2007
- 2007-05-15 IL IL183233A patent/IL183233A0/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5616599A (en) * | 1991-02-21 | 1997-04-01 | Sankyo Company, Limited | Angiotensin II antagosist 1-biphenylmethylimidazole compounds and their therapeutic use |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT509493B1 (en) * | 2006-09-15 | 2012-01-15 | Daiichi Sankyo Co Ltd | SOLID MEDICAMENT OF OLMESARTAN MEDOXOMIL AND AMLODIPIN |
| US8735598B2 (en) | 2008-06-09 | 2014-05-27 | Daiichi Sankyo Company, Limited | Method for producing 1-biphenylmethylimidazole compound |
| EP2426126A4 (en) * | 2009-04-28 | 2012-10-17 | Daiichi Sankyo Co Ltd | Method for producing olmesartan medoxomil |
| KR20120006512A (en) | 2009-04-28 | 2012-01-18 | 다이이찌 산쿄 가부시키가이샤 | Method for producing olmesartan medoxomil |
| EP2426126A1 (en) * | 2009-04-28 | 2012-03-07 | Daiichi Sankyo Company, Limited | Method for producing olmesartan medoxomil |
| WO2010126013A1 (en) | 2009-04-28 | 2010-11-04 | 第一三共株式会社 | Method for producing olmesartan medoxomil |
| WO2010126014A1 (en) | 2009-04-28 | 2010-11-04 | 第一三共株式会社 | Novel solvate crystals |
| US8859600B2 (en) | 2009-04-28 | 2014-10-14 | Daiichi Sankyo Company, Limited | Acetone solvate crystals of trityl olmesartan medoxomil |
| US8933241B2 (en) | 2009-04-28 | 2015-01-13 | Daiichi Sankyo Company, Limited | Method for producing olmesartan medoxomil |
| KR101676512B1 (en) | 2009-04-28 | 2016-11-15 | 다이이찌 산쿄 가부시키가이샤 | Method for producing olmesartan medoxomil |
| WO2012069025A1 (en) | 2010-11-24 | 2012-05-31 | Zentiva, K.S. | (5-methyl-2-oxo-1,3-dioxol-4-ylmethyl)-4-(1-hydroxy-1-methyl-propyl)-2-propyl-1-[2'- (1h-tetrazol-5-yl)biphenyl-4-yl-methyl]imidazole-5-carboxylate as an impurity of olmesartan medoxomil and a method of its preparation |
| WO2013021312A1 (en) * | 2011-08-05 | 2013-02-14 | Lupin Limited | Process for the preparation of olmesartan medoxomil |
| US8981110B2 (en) | 2011-08-05 | 2015-03-17 | Lupin Limited | Process for the preparation of olmesartan medoxomil |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1716139A1 (en) | 2006-11-02 |
| JP2007526342A (en) | 2007-09-13 |
| CA2592160A1 (en) | 2006-07-13 |
| US7563814B2 (en) | 2009-07-21 |
| US20060149078A1 (en) | 2006-07-06 |
| KR20090108739A (en) | 2009-10-16 |
| IL183233A0 (en) | 2007-08-19 |
| CN101094850A (en) | 2007-12-26 |
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