WO2013042067A1 - Procédé de préparation d'un sel de potassium de l'azilsartan médoxomil - Google Patents
Procédé de préparation d'un sel de potassium de l'azilsartan médoxomil Download PDFInfo
- Publication number
- WO2013042067A1 WO2013042067A1 PCT/IB2012/055002 IB2012055002W WO2013042067A1 WO 2013042067 A1 WO2013042067 A1 WO 2013042067A1 IB 2012055002 W IB2012055002 W IB 2012055002W WO 2013042067 A1 WO2013042067 A1 WO 2013042067A1
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- WO
- WIPO (PCT)
- Prior art keywords
- potassium
- azilsartan medoxomil
- potassium salt
- ketone
- process according
- Prior art date
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- 239000003861 C09CA09 - Azilsartan medoxomil Substances 0.000 title claims abstract description 40
- 229960001211 azilsartan medoxomil Drugs 0.000 title claims abstract description 40
- QJFSABGVXDWMIW-UHFFFAOYSA-N azilsartan medoxomil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C=3NC(=O)ON=3)C(OCC)=NC2=CC=CC=1C(=O)OCC=1OC(=O)OC=1C QJFSABGVXDWMIW-UHFFFAOYSA-N 0.000 title claims abstract description 40
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical group CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 25
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 22
- 239000011541 reaction mixture Substances 0.000 claims description 22
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 11
- 239000011591 potassium Substances 0.000 claims description 11
- 229910052700 potassium Inorganic materials 0.000 claims description 11
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 7
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 7
- 150000002576 ketones Chemical class 0.000 claims description 7
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 claims description 4
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 4
- HYTRYEXINDDXJK-UHFFFAOYSA-N Ethyl isopropyl ketone Chemical compound CCC(=O)C(C)C HYTRYEXINDDXJK-UHFFFAOYSA-N 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical group [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 239000004260 Potassium ascorbate Substances 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229960004109 potassium acetate Drugs 0.000 claims description 2
- 235000019275 potassium ascorbate Nutrition 0.000 claims description 2
- 229940017794 potassium ascorbate Drugs 0.000 claims description 2
- 235000010235 potassium benzoate Nutrition 0.000 claims description 2
- 229940103091 potassium benzoate Drugs 0.000 claims description 2
- 239000004300 potassium benzoate Substances 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- CONVKSGEGAVTMB-RXSVEWSESA-M potassium-L-ascorbate Chemical compound [K+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] CONVKSGEGAVTMB-RXSVEWSESA-M 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000005485 Azilsartan Substances 0.000 description 4
- 229960002731 azilsartan Drugs 0.000 description 4
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- IHWFKDWIUSZLCJ-UHFFFAOYSA-M azilsartan kamedoxomil Chemical compound [K+].C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C=3[N-]C(=O)ON=3)C(OCC)=NC2=CC=CC=1C(=O)OCC=1OC(=O)OC=1C IHWFKDWIUSZLCJ-UHFFFAOYSA-M 0.000 description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- -1 for example Chemical compound 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- XXCNLQUMVCHYSI-UHFFFAOYSA-N 2-[2-ethoxy-3-[[4-[2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazol-4-yl]-3-nitro-6-sulfobenzoic acid Chemical compound CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NOC(=O)N5)C6=C(C=CC(=C6C(=O)O)S(=O)(=O)O)[N+](=O)[O-] XXCNLQUMVCHYSI-UHFFFAOYSA-N 0.000 description 1
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000003087 receptor blocking agent Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Definitions
- the present invention relates to a process for the preparation of potassium salt of azilsartan medoxomil.
- Azilsartan medoxomil potassium is chemically described as (5-methyl-2-oxo-l,3- dioxol-4-yl)methyl 2-ethoxy- 1- ⁇ [2'-(5-oxo-4,5-dihydro- l,2,4-oxadiazol-3-yl)biphenyl- 4yl]methyl ⁇ -lH-benzimidazole-7-carboxylate monopotassium salt of Formula I.
- medoxomil is an angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
- ARB angiotensin II receptor blocker
- a process for the preparation of azilsartan medoxomil potassium is purportedly described in U.S. Patent No. 7, 157,584.
- Processes for the preparation of azilsartan medoxomil are purportedly described in U.S. Patent Nos. 7, 157,584 and 7,572,920 and in European Patent No. EP 2 1 19 715.
- the present invention provides a process for the preparation of a potassium salt of azilsartan medoxomil.
- Figure 1 depicts the X-ray powder diffraction pattern (XRPD) of the potassium salt of azilsartan medoxomil obtained according to Example 2.
- Figure 1A provides the table of values for the XRPD pattern depicted in Figure 1.
- Figure 2 depicts the X-ray powder diffraction pattern (XRPD) of the potassium salt of azilsartan medoxomil obtained according to Example 3.
- Figure 2A provides the table of values for the XRPD pattern depicted in Figure 2.
- Figure 3 depicts the X-ray powder diffraction pattern (XRPD) of the potassium salt of azilsartan medoxomil obtained according to the comparative example.
- Figure 3 A provides the table of values for the XRPD pattern depicted in Figure 3. Detailed Description of the Invention
- An aspect of the present invention provides a process for the preparation of potassium salt of azilsartan medoxomil, wherein the process comprises:
- Azilsartan medoxomil is reacted with a potassium source in the presence of at least one C4-9 ketone solvent.
- the at least one C4-9 ketone solvent may be methyl ethyl ketone, methyl isobutyl ketone, methyl isopropyl ketone, ethyl isopropyl ketone, butanone or acetophenone, for example, methyl ethyl ketone or methyl isobutyl ketone.
- the potassium source may be organic or inorganic in nature.
- An inorganic potassium source may be potassium hydroxide, potassium carbonate or potassium bicarbonate.
- An organic potassium source may be potassium acetate, potassium ascorbate, potassium benzoate, or potassium 2-ethylhexanoate, for example, potassium 2- ethylhexanoate.
- Treatment of azilsartan medoxomil with a potassium source in the presence of at least one C4-9 ketone solvent may be carried out at -20°C to 50°C, for example, at 0°C to 30°C. Treatment may be carried out for about 2 hours to about 6 hours.
- the potassium salt of azilsartan medoxomil may be isolated by filtration, distillation, decantation, vacuum drying, evaporation or a combination thereof.
- the polymorphic form of a potassium salt of azilsartan medoxomil obtained by the present invention is designated as Form I.
- the polymorphic Form I of a potassium salt of azilsartan medoxomil prepared by the invention has substantially the same XRPD (X-ray powder diffraction pattern) pattern as depicted in Figure 1 or Figure 2.
- the polymorphic Form I of a potassium salt of azilsartan medoxomil is characterized by an XRPD pattern comprising interplanar spacing (d) values substantially at 14.25, 6.62, 6.1 1, 6.00, 4.74, 3.91 and 3.74 A.
- the polymorphic Form I of potassium salt of azilsartan medoxomil is further characterized by an XRPD pattern comprising interplanar spacing (d) values substantially at 14.25, 13.23, 6.98, 6.62, 6.30, 6.11, 6.00, 5.53, 5.40, 5.1 1, 4.99, 4.89, 4.74, 4.38, 4.15, 3.91, 3.82, 3.74, 3.69, 3.58, 3.48, 3.32, 3.30, 3.24, 3.17, 3.09, 3.06, 2.90, 2.86, 2.81, 2.71 and 2.65 A.
- the polymorphic Form I of a potassium salt of azilsartan medoxomil of the present invention may be used for developing pharmaceutical dosage forms comprising potassium salt of azilsartan medoxomil.
- the polymorphic Form I of a potassium salt of azilsartan medoxomil of the present invention may also be used for the treatment of hypertension comprising a step of administering to a patient in need thereof a therapeutically effective amount of a polymorphic Form I of potassium salt of azilsartan medoxomil.
- the azilsartan medoxomil starting material may be prepared by any method known in literature.
- XRPD of the samples were determined by using Panalytical X'Pert Pro X-Ray Powder Diffractometer in the range 3-40 degree 2 theta and under tube voltage and current of 45 Kv and 40 mA respectively. Copper radiation of wavelength 1.54 angstrom and Xceletor detector was used.
- Azilsartan medoxomil (2.0 g) was added to acetone (36 mL) at 20°C to 30°C and the reaction mixture was heated to 40°C. The reaction mixture was cooled to 0°C to 5°C. A solution of potassium-2-ethyl hexanoate (0.618 g) in acetone (7.3 mL) was dropwise added to the reaction mixture at 0°C to 5°C. The reaction mixture was stirred at 0°C to 5°C for 2 hours. The solid material precipitated out. The reaction mixture was further stirred for 4 hours. The reaction mixture was filtered at 0°C to 5°C and washed with acetone (4 mL) at 0°C to 5°C. The reaction mixture was dried under vacuum at 20°C to 30°C to obtain the title compound having X-ray powder diffraction pattern (XRPD) as depicted in Figure 3.
- XRPD X-ray powder diffraction pattern
- Dichloromethane (50 mL) was added to azilsartan (5 g) and triethylamine (2.33 g) at 20°C to 30°C and was stirred for 5 minutes. The reaction mixture was cooled to 5°C. A solution of 4-nitrobenzenesulfonyl chloride (2.91 g) in dichloromethane (10 mL) was added to the reaction mixture at 5°C to 10°C for 10 minutes to 15 minutes. The temperature of the reaction mixture was raised to 25°C and it was stirred for 1 hour. The reaction mixture was washed with saturated sodium bicarbonate solution (25 mL). The organic layer was recovered at 40°C under vacuum to obtain the title compound.
- the temperature of the reaction mixture was raised to 40°C to 45°C and it was stirred for 2 hours.
- the reaction mixture was cooled to 20°C to 30°C and was washed with saturated sodium bicarbonate solution (50 mL).
- the reaction mixture was washed with 2N hydrochloric acid solution (25 mL).
- the organic layer was recovered under vacuum at 25°C to 30°C.
- the solution was recrystallized from diisopropylether (50 mL) to obtain the title compound.
- Azilsartan medoxomil (4.0 g) was added to methyl ethyl ketone (40 mL) at 20°C to
- Azilsartan medoxomil (5.0 g) was added to methyl isobutyl ketone (50 mL) at 20°C to 30°C and was stirred for 5 minutes to 10 minutes. The reaction mixture was cooled to 0°C to 5°C. Potassium-2-ethyl hexanoate (1.33 g) was added to methyl isobutyl ketone (20 mL) at 20°C to 30°C. This solution was added to the reaction mixture at 0°C to 5°C for 5 minutes to 10 minutes. The solution precipitated immediately. The temperature of the reaction mixture was raised to 20°C to 30°C and it was stirred for 3 hours to 4 hours.
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Plural Heterocyclic Compounds (AREA)
Abstract
L'invention concerne un procédé de préparation d'un sel de potassium de l'azilsartan médoxomil.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2729DE2011 | 2011-09-20 | ||
| IN2729/DEL/2011 | 2011-09-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013042067A1 true WO2013042067A1 (fr) | 2013-03-28 |
Family
ID=47216375
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2012/055002 WO2013042067A1 (fr) | 2011-09-20 | 2012-09-20 | Procédé de préparation d'un sel de potassium de l'azilsartan médoxomil |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2013042067A1 (fr) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013124748A1 (fr) * | 2012-02-20 | 2013-08-29 | Alembic Pharmaceuticals Limited | Nouveaux polymorphes d'azilsartan médoxomil potassique |
| WO2013156005A1 (fr) * | 2012-04-19 | 2013-10-24 | Zentiva, K.S. | Procédé de préparation d'un sel de potassium d'azilsartan médoxomil de grande pureté |
| WO2013186792A3 (fr) * | 2012-06-11 | 2014-02-06 | Msn Laboratories Limited | Procédé de préparation de 2-éthoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4- oxadiazol-3-yl)biphényl-4-yl]méthyl}-lh-benzimidazole-7-carboxylate de (5-méthyl-2-oxo-l,3-dioxol-4-yl)méthyle et de ses sels |
| WO2014020381A1 (fr) * | 2012-08-01 | 2014-02-06 | Alembic Pharmaceuticals Limited | Forme cristalline inédite d'azilsartan médoxomil potassique |
| WO2014048404A1 (fr) * | 2012-09-26 | 2014-04-03 | Zentiva, K.S. | Procédé de préparation d'un sel de potassium d'azilsartan médoxomil hautement pur |
| WO2015051546A1 (fr) * | 2013-10-12 | 2015-04-16 | 杭州领业医药科技有限公司 | Formes cristallines de l'ester d'azilsartan et leur procédé de préparation |
| EP2870151A4 (fr) * | 2012-07-09 | 2016-03-23 | Hetero Research Foundation | Nouveaux polymorphes d'azilsartan |
| CN105949182A (zh) * | 2013-10-12 | 2016-09-21 | 杭州领业医药科技有限公司 | 阿齐沙坦酯的晶型及其制备方法 |
Citations (1)
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|---|---|---|---|---|
| US7157584B2 (en) | 2004-02-25 | 2007-01-02 | Takeda Pharmaceutical Company Limited | Benzimidazole derivative and use thereof |
-
2012
- 2012-09-20 WO PCT/IB2012/055002 patent/WO2013042067A1/fr active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7157584B2 (en) | 2004-02-25 | 2007-01-02 | Takeda Pharmaceutical Company Limited | Benzimidazole derivative and use thereof |
| US7572920B2 (en) | 2004-02-25 | 2009-08-11 | Takeda Pharmaceutical Company Limited | Benzimidazole derivative and use as a II receptor antagonist |
| EP2119715A1 (fr) | 2004-02-25 | 2009-11-18 | Takeda Pharmaceutical Company Limited | Dérivé de benzimidazole et son utilisation en tant qu'antagoniste de récepteur |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013124748A1 (fr) * | 2012-02-20 | 2013-08-29 | Alembic Pharmaceuticals Limited | Nouveaux polymorphes d'azilsartan médoxomil potassique |
| WO2013156005A1 (fr) * | 2012-04-19 | 2013-10-24 | Zentiva, K.S. | Procédé de préparation d'un sel de potassium d'azilsartan médoxomil de grande pureté |
| WO2013186792A3 (fr) * | 2012-06-11 | 2014-02-06 | Msn Laboratories Limited | Procédé de préparation de 2-éthoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4- oxadiazol-3-yl)biphényl-4-yl]méthyl}-lh-benzimidazole-7-carboxylate de (5-méthyl-2-oxo-l,3-dioxol-4-yl)méthyle et de ses sels |
| EP2870151A4 (fr) * | 2012-07-09 | 2016-03-23 | Hetero Research Foundation | Nouveaux polymorphes d'azilsartan |
| WO2014020381A1 (fr) * | 2012-08-01 | 2014-02-06 | Alembic Pharmaceuticals Limited | Forme cristalline inédite d'azilsartan médoxomil potassique |
| CN104662019A (zh) * | 2012-09-26 | 2015-05-27 | 赞蒂瓦有限合伙公司 | 制备阿齐沙坦奥美沙坦酯的高纯度钾盐的方法 |
| WO2014048404A1 (fr) * | 2012-09-26 | 2014-04-03 | Zentiva, K.S. | Procédé de préparation d'un sel de potassium d'azilsartan médoxomil hautement pur |
| EA028171B1 (ru) * | 2012-09-26 | 2017-10-31 | Зентива К.С. | Способ получения высокочистой калиевой соли азилсартана медоксомила |
| WO2015051546A1 (fr) * | 2013-10-12 | 2015-04-16 | 杭州领业医药科技有限公司 | Formes cristallines de l'ester d'azilsartan et leur procédé de préparation |
| CN105949182A (zh) * | 2013-10-12 | 2016-09-21 | 杭州领业医药科技有限公司 | 阿齐沙坦酯的晶型及其制备方法 |
| CN105949183A (zh) * | 2013-10-12 | 2016-09-21 | 杭州领业医药科技有限公司 | 阿齐沙坦酯的晶型及其制备方法 |
| CN105949183B (zh) * | 2013-10-12 | 2019-02-22 | 杭州领业医药科技有限公司 | 阿齐沙坦酯的晶型及其制备方法 |
| CN105949182B (zh) * | 2013-10-12 | 2019-03-19 | 杭州领业医药科技有限公司 | 阿齐沙坦酯的晶型及其制备方法 |
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