HRP20110013T1 - Postupak proizvodnje ezetimiba i međuprodukti korišteni u tom postupku - Google Patents
Postupak proizvodnje ezetimiba i međuprodukti korišteni u tom postupku Download PDFInfo
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- HRP20110013T1 HRP20110013T1 HR20110013T HRP20110013T HRP20110013T1 HR P20110013 T1 HRP20110013 T1 HR P20110013T1 HR 20110013 T HR20110013 T HR 20110013T HR P20110013 T HRP20110013 T HR P20110013T HR P20110013 T1 HRP20110013 T1 HR P20110013T1
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- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 title claims abstract 5
- 229960000815 ezetimibe Drugs 0.000 title claims abstract 5
- 238000004519 manufacturing process Methods 0.000 title claims abstract 4
- 238000000034 method Methods 0.000 title claims abstract 4
- 239000000543 intermediate Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 34
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims abstract 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 3
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims abstract 2
- XSSTWZINYCULLM-UHFFFAOYSA-N 4-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]butanoic acid Chemical compound C=1C=C(F)C=CC=1C1(CCCC(=O)O)OCCO1 XSSTWZINYCULLM-UHFFFAOYSA-N 0.000 claims abstract 2
- 230000010933 acylation Effects 0.000 claims abstract 2
- 238000005917 acylation reaction Methods 0.000 claims abstract 2
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000003054 catalyst Substances 0.000 claims abstract 2
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract 2
- 150000002466 imines Chemical class 0.000 claims abstract 2
- -1 oxazolidinone compound Chemical class 0.000 claims abstract 2
- DURKZLMXWDUBFD-UHFFFAOYSA-N C(CO)O.FC1=CC=C(C(=O)CCCC(=O)O)C=C1 Chemical compound C(CO)O.FC1=CC=C(C(=O)CCCC(=O)O)C=C1 DURKZLMXWDUBFD-UHFFFAOYSA-N 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 238000006317 isomerization reaction Methods 0.000 claims 1
- 230000001681 protective effect Effects 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 230000007704 transition Effects 0.000 claims 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 abstract 3
- ZBQROUOOMAMCQW-UHFFFAOYSA-N 5-(4-fluorophenyl)-5-oxopentanoic acid Chemical compound OC(=O)CCCC(=O)C1=CC=C(F)C=C1 ZBQROUOOMAMCQW-UHFFFAOYSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 239000007795 chemical reaction product Substances 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Cephalosporin Compounds (AREA)
- General Factory Administration (AREA)
- Management, Administration, Business Operations System, And Electronic Commerce (AREA)
- Multi-Process Working Machines And Systems (AREA)
Abstract
Postupak proizvodnje ezetimiba Formule I naznačen time, da obuhvaća sljedeće korake: a) pretvaranje 4-(4-fluorobenzoil)-butirička kiselina etilen-glikola Formule II u4-[2-(4-fluoro-fenil)-[1,3]dioksolane-2-il]-butiričku kiselinu Formule IV preko nepripremljenog prijelaznog spoja Formule III, b) acilacija kiralnog spoja Formule V sa spojem Formule IV kako bi se dobio derivat aciliranog oksazolidinona Formule VI, pri čemu je spoj Formule V odabran od spojeva s Formulama Va, Vb, Vc, ili Vd i pri čemu R1, R2 i R3 predstavljaju: u slučaju Va: R1 = Ph, R2 = R3 = H, u slučaju Vb: R1 =R2 =R3 = Ph, u slučaju Vc: R1 = methyl, R2 = Ph, R3 = H, u slučaju Vd: R1 = izopropil, R2 = R3 = Ph, i pri čemu Ph predstavlja fenilnu skupinu, c) reagiranje kiselinskog oksazolidinonskog spoja Formule VI sa zaštićenim iminskim spojem FormuleVII, i izoliranje spoja Formule VIII, gdje R4 predstavlja sililnu skupinu, tecikliranje spoja Formule VIII kako bi se dobio derivat zaštićenog azetidinona opće Formule IX, d) hidroliziranje ketalne skupine spoja Formule IX kako bi se dobio spoj Formule X, e) enantio-selektivno reduciranje spoja opće Formule X kako bi se dobio spoj Formule XI, gdje je jedan od kiralnih spojeva CBS-oksazaborolidina s Formulama XIIa, XIIb, XIIc, ili XIId, odabran kao katalizator, i f) uklanjanje zaštitne sililne skupine spoja opće Formule XI da se dobije krajnji proizvod ezetimib Formule I, Patent sadrži još 7 patentnih zahtjeva.
Claims (8)
1. Postupak proizvodnje ezetimiba Formule I
[image]
naznačen time, da obuhvaća sljedeće korake:
a) pretvaranje 4-(4-fluorobenzoil)-butirička kiselina etilen-glikola Formule II u
4-[2-(4-fluoro-fenil)-[1,3]dioksolane-2-il]-butiričku kiselinu Formule IV preko nepripremljenog prijelaznog spoja Formule III,
[image]
b) acilacija kiralnog spoja Formule V sa spojem Formule IV kako bi se dobio derivat aciliranog oksazolidinona Formule VI,
[image]
pri čemu je spoj Formule V odabran od spojeva s Formulama Va, Vb, Vc, ili Vd
[image]
i pri čemu R1, R2 i R3 predstavljaju:
u slučaju Va: R1 = Ph, R2 = R3 = H,
u slučaju Vb: R1 =R2 =R3 = Ph,
u slučaju Vc: R1 = methyl, R2 = Ph, R3 = H,
u slučaju Vd: R1 = izopropil, R2 = R3 = Ph,
i pri čemu Ph predstavlja fenilnu skupinu,
c) reagiranje kiselinskog oksazolidinonskog spoja Formule VI sa zaštićenim iminskim spojem FormuleVII, i izoliranje spoja Formule VIII, gdje R4 predstavlja sililnu skupinu, te
[image]
cikliranje spoja Formule VIII kako bi se dobio derivat zaštićenog azetidinona opće Formule IX,
[image]
d) hidroliziranje ketalne skupine spoja Formule IX kako bi se dobio spoj Formule X,
[image]
e) enantio-selektivno reduciranje spoja opće Formule X kako bi se dobio spoj Formule XI,
[image]
gdje je jedan od kiralnih spojeva CBS-oksazaborolidina s Formulama XIIa, XIIb, XIIc, ili XIId, odabran kao katalizator,
i
[image]
f) uklanjanje zaštitne sililne skupine spoja opće Formule XI da se dobije krajnji proizvod ezetimib Formule I,
[image]
2. Postupak za proizvodnju spoja Formule VIIIa
[image]
naznačen time, da obuhvaća izomerizaciju spoja Formule VIIIb u prisutnosti spoja Ti(IV),
[image]
3. Spoj Formule III
[image]
naznačen time, da R predstavlja skupinu -O-CH2-CH2-OH ili -H.
4. Spoj Formule VI,
[image]
naznačen time, da R1, R2 i R3 predstavljaju:
R1=Ph, R2=R3=H,
R1=R2=R3=Ph,
R1=metil, R2=Ph, R3=H, ili
R1=izopropil, R2=R3=Ph,
i gdje Ph=fenil.
5. Spoj Formule VIII,
[image]
naznačen time, da je značenje od R1, R2, i R3 neovisno Va, Vb, Vc, ili Vd kao što je određeno u zahtjevu 1, a R4 je sililna zaštitna skupina.
6. Spojevi opće Formule IX
[image]
naznačeni time, da R4 je sililna zaštitna skupina.
7. Spoj, naznačen time, da ima Formulu Xa
[image]
8. Spoj, naznačen time, da ima Formulu XIa
[image]
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU0501164A HUP0501164A2 (en) | 2005-12-20 | 2005-12-20 | New industrial process for the production of ezetimibe |
| PCT/HU2006/000116 WO2007072088A1 (en) | 2005-12-20 | 2006-12-18 | Process for the production of ezetimibe and intermediates used in this proces |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20110013T1 true HRP20110013T1 (hr) | 2011-02-28 |
Family
ID=37492156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20110013T HRP20110013T1 (hr) | 2005-12-20 | 2011-01-11 | Postupak proizvodnje ezetimiba i međuprodukti korišteni u tom postupku |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US8178665B2 (hr) |
| EP (1) | EP1963260B1 (hr) |
| CN (1) | CN101346349B (hr) |
| AT (1) | ATE486848T1 (hr) |
| CA (1) | CA2630737A1 (hr) |
| CY (1) | CY1111307T1 (hr) |
| DE (1) | DE602006018063D1 (hr) |
| DK (1) | DK1963260T3 (hr) |
| EA (1) | EA014331B1 (hr) |
| ES (1) | ES2354728T3 (hr) |
| HK (1) | HK1128156A1 (hr) |
| HR (1) | HRP20110013T1 (hr) |
| HU (2) | HUP0501164A2 (hr) |
| PL (1) | PL1963260T3 (hr) |
| PT (1) | PT1963260E (hr) |
| RS (1) | RS51613B (hr) |
| SI (1) | SI1963260T1 (hr) |
| WO (1) | WO2007072088A1 (hr) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7871998B2 (en) | 2003-12-23 | 2011-01-18 | Astrazeneca Ab | Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity |
| CA2591564A1 (en) | 2004-12-20 | 2006-06-29 | Schering Corporation | Process for the synthesis of azetidinones |
| UY29607A1 (es) | 2005-06-20 | 2007-01-31 | Astrazeneca Ab | Compuestos quimicos |
| SA06270191B1 (ar) | 2005-06-22 | 2010-03-29 | استرازينيكا ايه بي | مشتقات من 2- أزيتيدينون جديدة باعتبارها مثبطات لامتصاص الكوليسترول لعلاج حالات فرط نسبة الدهون في الدم |
| MY148538A (en) | 2005-06-22 | 2013-04-30 | Astrazeneca Ab | Novel 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions |
| CA2634648A1 (en) * | 2005-12-22 | 2007-10-25 | Medichem, S.A. | Processes for preparing intermediate compounds useful for the preparation of ezetimibe |
| EP2007718A2 (en) * | 2006-03-29 | 2008-12-31 | Medichem, S.A. | Processes for preparing ezetimibe and intermediate compounds useful for the preparation thereof |
| WO2007120824A2 (en) * | 2006-04-10 | 2007-10-25 | Teva Pharmaceutical Industries Ltd. | Processes for the synthesis of azetidinone |
| TW200811098A (en) | 2006-04-27 | 2008-03-01 | Astrazeneca Ab | Chemical compounds |
| JP2009503119A (ja) * | 2006-08-29 | 2009-01-29 | テバ ファーマシューティカル インダストリーズ リミティド | （３ｒ，４ｓ）−４−（４−ヒドロキシ保護−フェニル）−１−（４−フルオロフェニル）−３−［３−（４−フルオロフェニル）−３−オキソプロピル］アゼチジン−２−オンを精製する方法 |
| CZ302395B6 (cs) * | 2007-03-02 | 2011-04-27 | Zentiva, A. S. | Zpusob výroby (3R,4S)-1-(4-fluorfenyl)-3-[(3S)-3-(4-fluorfenyl)-3-hydroxypropyl)]-4-(4-hydroxyfenyl)-2-azetidinonu |
| CZ2007843A3 (cs) * | 2007-11-30 | 2009-06-10 | Zentiva, A. S. | Zpusob výroby (3R,4S)-1-(4-fluorfenyl)-3-[(3S)-3-(4-fluorfenyl)-3-hydroxypropyl)]-4-(4-hydroxyfenyl)-2-azetidinonu a jeho meziprodukty |
| CZ2008317A3 (cs) * | 2008-05-21 | 2009-12-02 | Zentiva, A. S. | Zpusob výroby (3R,4S)-1-(4-fluorfenyl)-3-[(3S)-3-(4-fluorfenyl)-3-hydroxypropyl)]-4-(4-hydroxyfenyl)-2-azetidinonu |
| AR074752A1 (es) * | 2008-12-17 | 2011-02-09 | Hanmi Pharm Ind Co Ltd | Metodo para preparar ezetimiba e intermediarios usados en la misma |
| US9388440B2 (en) | 2009-04-01 | 2016-07-12 | Mylan Laboratories Limited | Enzymatic process for the preparation of (S)-5-(4-fluoro-phenyl)-5-hydroxy-1morpholin-4-yl-pentan-1-one, an intermediate of Ezetimibe and further conversion to Ezetimibe |
| CN101935309B (zh) * | 2009-06-29 | 2013-11-13 | 上海特化医药科技有限公司 | 依泽替米贝的制备方法及其中间体 |
| US8781844B2 (en) | 2009-09-25 | 2014-07-15 | Nokia Corporation | Audio coding |
| EP2566497B1 (en) | 2010-05-04 | 2015-07-29 | Codexis, Inc. | Biocatalysts for ezetimibe synthesis |
| ES2372460B1 (es) | 2010-07-09 | 2012-11-16 | Moehs Ibérica S.L. | Nuevo método para la preparación de ezetimiba. |
| CN102477008B (zh) * | 2010-11-22 | 2014-05-21 | 沈阳药科大学 | 依泽替米贝的合成方法 |
| WO2012076030A1 (en) | 2010-12-10 | 2012-06-14 | Pharmathen S.A. | Process for the preparation of intermediate compounds useful in the preparation of ezetimibe |
| CN102731489B (zh) * | 2011-04-11 | 2016-10-26 | 天津药物研究院有限公司 | 一种依折麦布关键中间体的制备方法 |
| CN102952055A (zh) * | 2011-08-16 | 2013-03-06 | 凯瑞斯德生化(苏州)有限公司 | 一种依泽替米贝和其中间体的制备方法 |
| CN103204795B (zh) * | 2012-01-11 | 2016-12-14 | 重庆华邦胜凯制药有限公司 | 一种手性氮杂环丁酮类化合物的制备方法 |
| CN103896700B (zh) * | 2012-12-25 | 2015-12-23 | 浙江九洲药物科技有限公司 | 依泽替米贝手性中间体的制备方法 |
| CN103450065B (zh) * | 2013-07-15 | 2015-10-14 | 和鼎（南京）医药技术有限公司 | 制备依泽替米贝的方法 |
| CN103739537B (zh) * | 2013-12-24 | 2015-05-20 | 连云港恒运医药科技有限公司 | 依折麦布的新合成方法 |
| CN104892537B (zh) * | 2015-05-15 | 2018-07-17 | 江西施美药业股份有限公司 | 依折麦布中间体以及依折麦布的合成方法 |
| CN105566243B (zh) * | 2016-01-15 | 2017-10-31 | 齐鲁天和惠世制药有限公司 | 从依折麦布生产废液中回收(s)‑(+)‑4‑苯基‑2‑噁唑烷酮的方法 |
| CN107098841A (zh) * | 2016-02-19 | 2017-08-29 | 常州方楠医药技术有限公司 | 一种依折麦布的制备方法及该方法中所用的中间体 |
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| CN107488173B (zh) * | 2016-06-10 | 2021-05-04 | 山东新时代药业有限公司 | 一种依折麦布中间体及其合成方法 |
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| CN107488190B (zh) * | 2016-06-10 | 2021-07-02 | 山东新时代药业有限公司 | 一种依折麦布中间体及其制备方法 |
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| CN116283948A (zh) * | 2023-02-24 | 2023-06-23 | 江苏阿尔法药业股份有限公司 | 一种依折麦布中间体的合成方法 |
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| US5919672A (en) * | 1998-10-02 | 1999-07-06 | Schering Corporation | Resolution of trans-2-(alkoxycarbonylethyl)-lactams useful in the synthesis of 1-(4-fluoro-phenyl)-3(R)- (S)-hydroxy-3-(4-fluorophenyl)-propyl!-4(S)-(4-hydroxyphenyl)-2-azetidinone |
| AR025144A1 (es) * | 1998-12-07 | 2002-11-13 | Schering Corp | Proceso para preparar azetidinonas, proceso para preparar compuestos intermediarios asi como dichos compuestos intermediarios |
| US6207822B1 (en) * | 1998-12-07 | 2001-03-27 | Schering Corporation | Process for the synthesis of azetidinones |
| WO2002079174A2 (en) * | 2001-03-28 | 2002-10-10 | Schering Corporation | Enantioselective synthesis of azetidinone intermediate compounds |
| WO2005066120A2 (en) | 2003-12-30 | 2005-07-21 | Ranbaxy Laboratories Limited | Process for asymmetric synthesis of hydroxy-alkyl substituted azetidinone derivatives |
| EP1893570A4 (en) * | 2005-06-22 | 2009-12-23 | Reddy Manne Satynarayana | IMPROVED PROCESS FOR THE PREPARATION OF EZETIMIBE |
| MX2007005493A (es) * | 2005-09-08 | 2007-09-11 | Teva Pharma | Procesos para la preparacion de (3r,4s)-4-((4-benciloxi)fenil)-1- (4-fluorofenil)-3-((s)-3-(4-fluorofenil)-3-hidroxipropil-2- azetidinona, un intermedio para la sintesis de ezetimibe. |
| CA2634648A1 (en) * | 2005-12-22 | 2007-10-25 | Medichem, S.A. | Processes for preparing intermediate compounds useful for the preparation of ezetimibe |
| EP2007718A2 (en) * | 2006-03-29 | 2008-12-31 | Medichem, S.A. | Processes for preparing ezetimibe and intermediate compounds useful for the preparation thereof |
| WO2007120824A2 (en) * | 2006-04-10 | 2007-10-25 | Teva Pharmaceutical Industries Ltd. | Processes for the synthesis of azetidinone |
| JP2009503119A (ja) * | 2006-08-29 | 2009-01-29 | テバ ファーマシューティカル インダストリーズ リミティド | （３ｒ，４ｓ）−４−（４−ヒドロキシ保護−フェニル）−１−（４−フルオロフェニル）−３−［３−（４−フルオロフェニル）−３−オキソプロピル］アゼチジン−２−オンを精製する方法 |
| CN102285906B (zh) * | 2007-01-24 | 2014-11-19 | 克尔克公司 | 依泽替米贝的制备方法和其的衍生物 |
| CZ302395B6 (cs) * | 2007-03-02 | 2011-04-27 | Zentiva, A. S. | Zpusob výroby (3R,4S)-1-(4-fluorfenyl)-3-[(3S)-3-(4-fluorfenyl)-3-hydroxypropyl)]-4-(4-hydroxyfenyl)-2-azetidinonu |
| US20090047716A1 (en) * | 2007-06-07 | 2009-02-19 | Nurit Perlman | Reduction processes for the preparation of ezetimibe |
| US20080318920A1 (en) * | 2007-06-19 | 2008-12-25 | Protia, Llc | Deuterium-enriched ezetimibe |
| US20090093627A1 (en) * | 2007-08-30 | 2009-04-09 | Lorand Szabo | Process for preparing intermediates of ezetimibe by microbial reduction |
| CZ2007843A3 (cs) * | 2007-11-30 | 2009-06-10 | Zentiva, A. S. | Zpusob výroby (3R,4S)-1-(4-fluorfenyl)-3-[(3S)-3-(4-fluorfenyl)-3-hydroxypropyl)]-4-(4-hydroxyfenyl)-2-azetidinonu a jeho meziprodukty |
| CZ305066B6 (cs) * | 2008-02-25 | 2015-04-22 | Zentiva, K.S. | Způsob výroby (3R,4S)-1-(4-fluorfenyl)-3-[(3S)-3-(4-fluorfenyl)-3-hydroxypropyl)]-4-(4-hydroxyfenyl)-2-azetidinonu |
| CZ2008317A3 (cs) * | 2008-05-21 | 2009-12-02 | Zentiva, A. S. | Zpusob výroby (3R,4S)-1-(4-fluorfenyl)-3-[(3S)-3-(4-fluorfenyl)-3-hydroxypropyl)]-4-(4-hydroxyfenyl)-2-azetidinonu |
-
2005
- 2005-12-20 HU HU0501164A patent/HUP0501164A2/hu unknown
- 2005-12-20 HU HU0501164A patent/HU0501164D0/hu unknown
-
2006
- 2006-12-18 RS RS20100505A patent/RS51613B/en unknown
- 2006-12-18 EP EP06831516A patent/EP1963260B1/en active Active
- 2006-12-18 ES ES06831516T patent/ES2354728T3/es active Active
- 2006-12-18 EA EA200801548A patent/EA014331B1/ru unknown
- 2006-12-18 DK DK06831516.7T patent/DK1963260T3/da active
- 2006-12-18 PT PT06831516T patent/PT1963260E/pt unknown
- 2006-12-18 US US12/097,185 patent/US8178665B2/en not_active Expired - Fee Related
- 2006-12-18 CA CA002630737A patent/CA2630737A1/en not_active Abandoned
- 2006-12-18 AT AT06831516T patent/ATE486848T1/de active
- 2006-12-18 DE DE602006018063T patent/DE602006018063D1/de active Active
- 2006-12-18 WO PCT/HU2006/000116 patent/WO2007072088A1/en active Application Filing
- 2006-12-18 SI SI200630888T patent/SI1963260T1/sl unknown
- 2006-12-18 CN CN2006800485754A patent/CN101346349B/zh not_active Expired - Fee Related
- 2006-12-18 PL PL06831516T patent/PL1963260T3/pl unknown
-
2009
- 2009-06-30 HK HK09105859.0A patent/HK1128156A1/xx not_active IP Right Cessation
-
2010
- 2010-12-27 CY CY20101101193T patent/CY1111307T1/el unknown
-
2011
- 2011-01-11 HR HR20110013T patent/HRP20110013T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL1963260T3 (pl) | 2011-04-29 |
| CY1111307T1 (el) | 2015-08-05 |
| CA2630737A1 (en) | 2007-06-28 |
| PT1963260E (pt) | 2010-12-27 |
| CN101346349A (zh) | 2009-01-14 |
| EA014331B1 (ru) | 2010-10-29 |
| CN101346349B (zh) | 2011-04-20 |
| HK1128156A1 (en) | 2009-10-16 |
| EP1963260B1 (en) | 2010-11-03 |
| RS51613B (en) | 2011-08-31 |
| SI1963260T1 (sl) | 2011-02-28 |
| ES2354728T3 (es) | 2011-03-17 |
| HU0501164D0 (en) | 2006-02-28 |
| ATE486848T1 (de) | 2010-11-15 |
| US20090216009A1 (en) | 2009-08-27 |
| DE602006018063D1 (de) | 2010-12-16 |
| HUP0501164A2 (en) | 2007-07-30 |
| EA200801548A1 (ru) | 2008-10-30 |
| DK1963260T3 (da) | 2011-01-17 |
| WO2007072088A1 (en) | 2007-06-28 |
| EP1963260A1 (en) | 2008-09-03 |
| US8178665B2 (en) | 2012-05-15 |
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