WO2004046105A3 - Synthesis of 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids - Google Patents

Synthesis of 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids Download PDF

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Publication number
WO2004046105A3
WO2004046105A3 PCT/US2003/037026 US0337026W WO2004046105A3 WO 2004046105 A3 WO2004046105 A3 WO 2004046105A3 US 0337026 W US0337026 W US 0337026W WO 2004046105 A3 WO2004046105 A3 WO 2004046105A3
Authority
WO
WIPO (PCT)
Prior art keywords
dihydroxy
pyrrol
heptanoic acid
silylether
heptanoic
Prior art date
Application number
PCT/US2003/037026
Other languages
French (fr)
Other versions
WO2004046105A2 (en
Inventor
Jakob Oren
Ben-Zion Dolitzky
Zvi Harel
Nurit Perlman
Ramy Lidor-Hadas
Original Assignee
Teva Pharma
Jakob Oren
Ben-Zion Dolitzky
Zvi Harel
Nurit Perlman
Ramy Lidor-Hadas
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, Jakob Oren, Ben-Zion Dolitzky, Zvi Harel, Nurit Perlman, Ramy Lidor-Hadas filed Critical Teva Pharma
Priority to EP03786885A priority Critical patent/EP1480943A2/en
Priority to AU2003295684A priority patent/AU2003295684A1/en
Publication of WO2004046105A2 publication Critical patent/WO2004046105A2/en
Publication of WO2004046105A3 publication Critical patent/WO2004046105A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
    • C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
    • C07C215/10—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with one amino group and at least two hydroxy groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • 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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Atorvastatin and related 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids can be made by oxidation of a 3,5-dihydroxy-7-pyrrol-1-yl heptanol precursor from novel but readily accessible starting materials. Silylether-protected 7-amino-3,5-dihydroxy heptanoic acid esters undergo Paal Knorr reaction with 1,4-diketones to give valuable silylether-diprotected 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acid ester intermediates for preparing atorvastatin. The Paal Knorr reaction of ketal-proctected 7-amino-3R, 5R-dihydroxy heptanoic acid esters with 4-fluoro-α-(2-methyl-1-oxopropyl-Ϝ-oxo-N,β-diphenylbenzenebutanamide occurs in high yield with few side products when it is conducted in a low boiling point ether.
PCT/US2003/037026 2002-11-15 2003-11-17 Synthesis of 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids WO2004046105A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP03786885A EP1480943A2 (en) 2002-11-15 2003-11-17 Synthesis of 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids
AU2003295684A AU2003295684A1 (en) 2002-11-15 2003-11-17 Synthesis of 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US42634202P 2002-11-15 2002-11-15
US60/426,342 2002-11-15
US46611403P 2003-04-29 2003-04-29
US60/466,114 2003-04-29
US48044003P 2003-06-23 2003-06-23
US60/480,440 2003-06-23
US48338103P 2003-06-27 2003-06-27
US60/483,381 2003-06-27

Publications (2)

Publication Number Publication Date
WO2004046105A2 WO2004046105A2 (en) 2004-06-03
WO2004046105A3 true WO2004046105A3 (en) 2004-10-07

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/037026 WO2004046105A2 (en) 2002-11-15 2003-11-17 Synthesis of 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids

Country Status (3)

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EP (1) EP1480943A2 (en)
AU (1) AU2003295684A1 (en)
WO (1) WO2004046105A2 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2601111A1 (en) * 2005-03-14 2006-09-21 Pfizer Science And Technology Ireland Limited Preparation of an atorvastatin intermediate using a paal-knorr condensation
GB2424880A (en) * 2005-04-06 2006-10-11 Generics Crystalline forms of atorvastatin sodium, processes for their preparation and their use in inhibiting HMG-CoA reductase
SI22255A (en) * 2006-04-14 2007-10-31 Krka, Tovarna Zdravil, D.D., Novo Mesto New polymorphs of statine salts and their application in pharmaceutical formulations
US20090081801A1 (en) * 2007-08-15 2009-03-26 Vinod Kumar Kansal Process for synthesis of pyrrole derivative, an intermediate for atorvastatin
KR100850558B1 (en) 2008-01-02 2008-08-06 조동옥 Process for preparing useful in synthesis of atorvastatin
CN103184248B (en) * 2011-12-29 2016-02-10 杭州师范大学 The method of the pyrrole ring analog derivative that a kind of Enzyme catalyzed synthesis N-replaces
CN102796036B (en) * 2012-09-12 2014-06-04 江苏阿尔法药业有限公司 Preparation method of atorvastatin calcium
JP2021509907A (en) * 2018-01-09 2021-04-08 リガンド・ファーマシューティカルズ・インコーポレイテッド Acetal compounds and their therapeutic use
CN109232353A (en) * 2018-10-09 2019-01-18 河南师范大学 A kind of preparation method of Atorvastatin calcium condensation product
CN109232354A (en) * 2018-10-09 2019-01-18 河南师范大学 A kind of preparation method of high purity atorvastatin calcium raw material drug

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0330172A2 (en) * 1988-02-22 1989-08-30 Warner-Lambert Company Improved process for trans-6-[2-(substituted-pyrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
EP0436851A1 (en) * 1989-12-21 1991-07-17 ZAMBON GROUP S.p.A. Compounds active as inhibitors of the enzyme HMG-CoA reductase and pharmaceutical compositions containing them
WO2002055519A2 (en) * 2001-01-09 2002-07-18 Warner Lambert Co Novel 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
WO2003004450A1 (en) * 2001-07-06 2003-01-16 Ciba Specialty Chemicals Holding Inc. Process for the preparation of intermediates useful in the synthesis of statin derivatives especially 7-amino 3,5-dihydroxy heptanoic acid derivatives, and intermediates thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0330172A2 (en) * 1988-02-22 1989-08-30 Warner-Lambert Company Improved process for trans-6-[2-(substituted-pyrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
EP0436851A1 (en) * 1989-12-21 1991-07-17 ZAMBON GROUP S.p.A. Compounds active as inhibitors of the enzyme HMG-CoA reductase and pharmaceutical compositions containing them
WO2002055519A2 (en) * 2001-01-09 2002-07-18 Warner Lambert Co Novel 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
WO2003004450A1 (en) * 2001-07-06 2003-01-16 Ciba Specialty Chemicals Holding Inc. Process for the preparation of intermediates useful in the synthesis of statin derivatives especially 7-amino 3,5-dihydroxy heptanoic acid derivatives, and intermediates thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEN, BANG-CHI ET AL: "Synthesis of deuterium-labeled atorvastatin and its metabolites for use a internal standards in a LC/MS/MS method developed for quantitation of the drug and its metabolites in human serum", JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, vol. 43, no. 3, 2000, pages 261 - 270, XP002286571 *
ESCUDIER J-M ET AL: "Diastereoface Differentiation in Addition of Lithium Enolates to Chiral alpha,beta-Epoxyaldehydes", TETRAHEDRON, vol. 49, no. 24, 1993, pages 5253 - 5266, XP002278080 *
KARANEWSKY D S: "Synthetic Transformations of the Mevinic Acid Nucleus: Preparation of a Monocyclic Analogue of Compactin", TETRAHEDRON LETTERS, vol. 32, no. 32, 1991, pages 3911 - 3914, XP002278079 *

Also Published As

Publication number Publication date
AU2003295684A8 (en) 2004-06-15
EP1480943A2 (en) 2004-12-01
WO2004046105A2 (en) 2004-06-03
AU2003295684A1 (en) 2004-06-15

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