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MXPA03012045A - Proceso para preparar derivados del acido 7-amino sin 3,5-dihidroxi heptanoico a traves de derivados del acido 6-ciano sin 3,5-dihidroxi hexanoico. - Google Patents

Proceso para preparar derivados del acido 7-amino sin 3,5-dihidroxi heptanoico a traves de derivados del acido 6-ciano sin 3,5-dihidroxi hexanoico.

Info

Publication number
MXPA03012045A
MXPA03012045A MXPA03012045A MXPA03012045A MXPA03012045A MX PA03012045 A MXPA03012045 A MX PA03012045A MX PA03012045 A MXPA03012045 A MX PA03012045A MX PA03012045 A MXPA03012045 A MX PA03012045A MX PA03012045 A MXPA03012045 A MX PA03012045A
Authority
MX
Mexico
Prior art keywords
syn
acid derivatives
dihydroxy
preparation
cyano
Prior art date
Application number
MXPA03012045A
Other languages
English (en)
Inventor
Studer Martin
Original Assignee
Teva Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Teva Pharma filed Critical Teva Pharma
Publication of MXPA03012045A publication Critical patent/MXPA03012045A/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/30—Preparation of optical isomers
    • C07C227/32—Preparation of optical isomers by stereospecific synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
    • C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
    • C07C69/716—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrrole Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

(ver formula) La invencion se relaciona con metodos de sintesis novedosos para la preparacion de los intermedios, que son adecuados para la preparacion de derivados de estatinas, especialmente con metodos de sintesis novedosos del intermedio de la formula VI en donde Ra y Rc son cada uno independientemente del otro, hidrogeno o un grupo protector de hidroxi o juntos son un grupo protector de hidroxi, y Rb es un grupo protector de carboxi, cuyos metodos se llevan a cabo mediante la conversion del intermedio de la f6rmula XIX en donde Ra y Rc son cada uno independientemente del otro hidrogeno o un grupo protector de hidroxi y Rb es un grupo protector de carboxi.
MXPA03012045A 2001-07-06 2002-07-02 Proceso para preparar derivados del acido 7-amino sin 3,5-dihidroxi heptanoico a traves de derivados del acido 6-ciano sin 3,5-dihidroxi hexanoico. MXPA03012045A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP01810670 2001-07-06
PCT/EP2002/007309 WO2003004456A1 (en) 2001-07-06 2002-07-02 Process for the preparation of 7-amino syn 3,5-dihydroxy heptanoic acid derivatives via 6-cyano syn 3,5-dihydroxy hexanoic acid derivatives

Publications (1)

Publication Number Publication Date
MXPA03012045A true MXPA03012045A (es) 2004-03-29

Family

ID=41547052

Family Applications (1)

Application Number Title Priority Date Filing Date
MXPA03012045A MXPA03012045A (es) 2001-07-06 2002-07-02 Proceso para preparar derivados del acido 7-amino sin 3,5-dihidroxi heptanoico a traves de derivados del acido 6-ciano sin 3,5-dihidroxi hexanoico.

Country Status (11)

Country Link
US (2) US7199261B2 (es)
EP (1) EP1406860A1 (es)
JP (1) JP2004533482A (es)
CA (1) CA2451159A1 (es)
HR (1) HRP20040116A2 (es)
HU (1) HUP0401014A2 (es)
IL (1) IL159719A0 (es)
MX (1) MXPA03012045A (es)
PL (1) PL366610A1 (es)
SK (1) SK802004A3 (es)
WO (1) WO2003004456A1 (es)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7300775B2 (en) 1999-12-29 2007-11-27 Verenium Corporation Methods for producing α-substituted carboxylic acids using nitrilases and strecker reagents
US7521216B2 (en) 1999-12-29 2009-04-21 Verenium Corporation Nitrilases and methods for making and using them
US7608445B1 (en) 1999-12-29 2009-10-27 Verenium Corporation Nitrilases, nucleic acids encoding them and methods for making and using them
WO2002057229A1 (en) 2001-01-19 2002-07-25 Biocon India Limited FORM V CRYSTALLINE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1- HEPTANOIC ACID HEMI CALCIUM SALT. (ATORVASTATIN)
IL159719A0 (en) * 2001-07-06 2004-06-20 Teva Pharma Process for the preparation of 7-amino syn 3,5-dihydroxy heptanoic acid derivatives via 6-cyano syn 3,5-dihydroxy hexanoic acid derivatives
PT1404642E (pt) 2001-07-06 2010-03-29 Basf Se Processo para a preparação de derivados do ácido 7-amino sin 3,5-dihidroxi heptanoico, intermediários respectivos e métodos para a sua preparação
US7361772B2 (en) 2001-08-16 2008-04-22 Biocon Limited Process for the production of atorvastatin calcium
IL164020A0 (en) 2002-03-18 2005-12-18 Biocon Ltd A process for the preparation of amorphous hmg-coareductase inhibitors
AU2003251523A1 (en) 2002-06-13 2003-12-31 Diversa Corporation Processes for making (r)-ethyl 4-cyano-3-hydroxybutyric acid
US7179942B2 (en) 2002-07-05 2007-02-20 Bicon Limited Halo-substituted active methylene compounds
ES2323366T3 (es) 2003-04-22 2009-07-14 Biocon Limited Procedimiento novedoso para la reduccion estereoselectiva de beta-cetoesteres.
AU2003272080A1 (en) 2003-09-18 2005-04-06 Biocon Limited Novel process for the preparation of tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate
EP2115153B1 (en) 2007-03-01 2013-06-05 BP Corporation North America Inc. Nitrilases, nucleic acids encoding them and methods for making and using them
US8728504B2 (en) 2010-02-05 2014-05-20 Basf Se Process for solubilizing hydrophobic active ingredients in aqueous medium
US8877221B2 (en) 2010-10-27 2014-11-04 Warsaw Orthopedic, Inc. Osteoconductive matrices comprising calcium phosphate particles and statins and methods of using the same
US9107983B2 (en) 2010-10-27 2015-08-18 Warsaw Orthopedic, Inc. Osteoconductive matrices comprising statins
US9308190B2 (en) 2011-06-06 2016-04-12 Warsaw Orthopedic, Inc. Methods and compositions to enhance bone growth comprising a statin

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5003080A (en) 1988-02-22 1991-03-26 Warner-Lambert Company Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis
US5097045A (en) * 1989-02-01 1992-03-17 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
IT1226726B (it) 1988-07-29 1991-02-05 Zambon Spa Composti attivi come inibitori della biosintesi del colesterolo.
JPH02115234A (ja) * 1988-10-26 1990-04-27 Tdk Corp 架橋ポリフッ化ビニリデンの製造方法
US4994602A (en) 1989-02-27 1991-02-19 Takasago International Corporation Process for preparing optically active 6-t-butyoxy-3,5-dihydroxyhexanoic esters
FI94339C (fi) * 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
IT1237792B (it) 1989-12-21 1993-06-17 Zambon Spa Composti attivi come inibitori dell'enzima hmg-coa reduttasi
US5248793A (en) * 1990-10-17 1993-09-28 Warner-Lambert Company Process for the synthesis of (4R-cis)-1,1-dimethylethyl 6-iodomethyl or 6-(phenyl-substituted)sulfonyloxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate
US5155251A (en) * 1991-10-11 1992-10-13 Warner-Lambert Company Process for the synthesis of (5R)-1,1-dimethylethyl-6-cyano-5-hydroxy-3-oxo-hexanoate
US5278313A (en) * 1992-03-27 1994-01-11 E. R. Squibb & Sons, Inc. Process for the preparation of 1,3-dioxane derivatives useful in the preparation of HMG-COA reductase inhibitors
CA2150372C (en) * 1993-01-19 2002-08-20 Nancy L. Mills Stable oral ci-981 formulation and process of preparing same
US5298627A (en) * 1993-03-03 1994-03-29 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
JP3652394B2 (ja) * 1995-01-27 2005-05-25 高砂香料工業株式会社 Ｎ−置換−７−アミノ−５−ヒドロキシ−３−オキソヘプタン酸誘導体およびその製造法
TR199900191T2 (xx) * 1996-07-29 1999-04-21 Warner-Lambert Company (S)-3,4-Dihidroksibutirik asitin korumal� esterlerinin sentezi i�in geli�tirilmi� proses.
US5908953A (en) * 1996-12-18 1999-06-01 Mitsubishi Chemical Corporation Method for producing (R)-4-cyano-3-hydroxybutyric acid lower alkyl ester
JP2001526256A (ja) * 1997-12-19 2001-12-18 ワーナー−ランバート・エクスポート・リミテッド １，３−ジオールの合成方法
HUP0103659A3 (en) * 1998-04-30 2003-01-28 Kaneka Corp Process for producing 6-cyanomethyl-1,3-dioxane-4-acetic acid derivatives
ATE486068T1 (de) * 1998-08-05 2010-11-15 Kaneka Corp Verfahren zur herstellung optisch aktiver 2-ä6- (hydroxymethyl)-1,3-dioxan-4-ylü-essigsäure- derivate
DE19920784A1 (de) 1999-05-05 2000-11-09 Bayer Ag Stilbenaufheller
HU227840B1 (en) 1999-05-06 2012-05-02 Egis Gyogyszergyar Nyilvanosan M Kod Ruszvunytarsasag Intermediates of atorvastatin synthesis and process for producing them
US6476235B2 (en) * 2001-01-09 2002-11-05 Warner-Lambert Company Process for the synthesis of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide
US6417374B1 (en) * 2001-02-15 2002-07-09 Council Of Scientific & Industrial Research Process for the preparation of beta hydroxy-delta lactone using novel intermediates
US6777443B2 (en) * 2001-05-15 2004-08-17 Novartis Ag Dipeptide derivatives
IL159719A0 (en) * 2001-07-06 2004-06-20 Teva Pharma Process for the preparation of 7-amino syn 3,5-dihydroxy heptanoic acid derivatives via 6-cyano syn 3,5-dihydroxy hexanoic acid derivatives
KR100657212B1 (ko) 2004-04-29 2006-12-14 엔자이텍 주식회사 라세믹 에스테르로부터 광학활성 에스테르 유도체와 이의 산의 제조 방법
US20090221839A1 (en) 2005-09-09 2009-09-03 Pfizer Inc. Preparation of an Atorvastatin Intermediate

Also Published As

Publication number Publication date
HUP0401014A2 (hu) 2004-08-30
WO2003004456A1 (en) 2003-01-16
US7199261B2 (en) 2007-04-03
JP2004533482A (ja) 2004-11-04
CA2451159A1 (en) 2003-01-16
HRP20040116A2 (en) 2004-10-31
US20050033086A1 (en) 2005-02-10
EP1406860A1 (en) 2004-04-14
US20070142662A1 (en) 2007-06-21
PL366610A1 (en) 2005-02-07
US7692034B2 (en) 2010-04-06
IL159719A0 (en) 2004-06-20
SK802004A3 (en) 2004-10-05

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