CA2432064A1 - 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 - Google Patents

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 Download PDF

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CA2432064A1
CA2432064A1 CA002432064A CA2432064A CA2432064A1 CA 2432064 A1 CA2432064 A1 CA 2432064A1 CA 002432064 A CA002432064 A CA 002432064A CA 2432064 A CA2432064 A CA 2432064A CA 2432064 A1 CA2432064 A1 CA 2432064A1
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Prior art keywords
pyran
fluorophenyl
pyrrole
tetrahydro
oxo
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CA002432064A
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CA2432064C (en
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Donald Eugene Butler
Randall Lee Dejong
Jade Douglas Nelson
Michael Gerard Pamment
Timothy Lee Stuk
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Warner Lambert Co LLC
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Donald Eugene Butler
Randall Lee Dejong
Jade Douglas Nelson
Michael Gerard Pamment
Timothy Lee Stuk
Warner-Lambert Company Llc
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Priority to CA002538995A priority Critical patent/CA2538995A1/en
Publication of CA2432064A1 publication Critical patent/CA2432064A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • 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
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • C07D207/416—2,5-Pyrrolidine-diones 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 other ring carbon atoms
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pyrrole Compounds (AREA)
  • Catalysts (AREA)

Abstract

An improved process for the preparation 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 (see above formula) by a novel synthesis is described where methyl cyanoacetate is converted in eight operations or fewer to the desired product, as well as other valuable intermediates used in the process.
CA002432064A 2001-01-09 2001-12-27 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 Expired - Fee Related CA2432064C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA002538995A CA2538995A1 (en) 2001-01-09 2001-12-27 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

Applications Claiming Priority (3)

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US26050501P 2001-01-09 2001-01-09
US60/260,505 2001-01-09
PCT/IB2001/002729 WO2002055519A2 (en) 2001-01-09 2001-12-27 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

Related Child Applications (1)

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CA002538995A Division CA2538995A1 (en) 2001-01-09 2001-12-27 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

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CA2432064A1 true CA2432064A1 (en) 2002-07-18
CA2432064C CA2432064C (en) 2007-09-11

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US (7) US6476235B2 (en)
EP (1) EP1353917B1 (en)
JP (2) JP4190285B2 (en)
KR (3) KR100833911B1 (en)
CN (4) CN101024626A (en)
AR (1) AR035680A1 (en)
AT (1) ATE358126T1 (en)
BR (1) BR0116739A (en)
CA (1) CA2432064C (en)
CY (1) CY1106590T1 (en)
CZ (1) CZ20031893A3 (en)
DE (1) DE60127583T2 (en)
DK (1) DK1353917T3 (en)
ES (1) ES2282200T3 (en)
HK (2) HK1060572A1 (en)
HU (1) HUP0302647A3 (en)
IL (4) IL156461A0 (en)
MX (1) MXPA03005284A (en)
PL (1) PL365283A1 (en)
PT (1) PT1353917E (en)
RU (1) RU2244714C1 (en)
TW (1) TWI293073B (en)
WO (1) WO2002055519A2 (en)
YU (1) YU49003A (en)
ZA (1) ZA200304684B (en)

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US20020133026A1 (en) 2002-09-19
AU2002222430B2 (en) 2007-05-17
JP4190285B2 (en) 2008-12-03
HUP0302647A3 (en) 2009-03-30
KR100677008B1 (en) 2007-02-01
HK1084114A1 (en) 2006-07-21
KR20060114395A (en) 2006-11-06
KR20030065594A (en) 2003-08-06
CN100351252C (en) 2007-11-28
IL189357A0 (en) 2008-06-05
WO2002055519A3 (en) 2002-09-19
US20070032664A1 (en) 2007-02-08
IL189358A0 (en) 2008-06-05
KR20060015698A (en) 2006-02-17
ZA200304684B (en) 2004-06-28
US7361771B2 (en) 2008-04-22
CN1696129A (en) 2005-11-16
HK1060572A1 (en) 2004-08-13
US7399773B2 (en) 2008-07-15
TWI293073B (en) 2008-02-01
ES2282200T3 (en) 2007-10-16
CN1907984A (en) 2007-02-07
IL189359A0 (en) 2008-06-05
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ATE358126T1 (en) 2007-04-15
AR035680A1 (en) 2004-06-23
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US6476235B2 (en) 2002-11-05
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CA2432064C (en) 2007-09-11
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