WO2002055519A3 - 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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Publication number
WO2002055519A3
WO2002055519A3 PCT/IB2001/002729 IB0102729W WO02055519A3 WO 2002055519 A3 WO2002055519 A3 WO 2002055519A3 IB 0102729 W IB0102729 W IB 0102729W WO 02055519 A3 WO02055519 A3 WO 02055519A3
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WO
WIPO (PCT)
Prior art keywords
pyran
fluorophenyl
pyrrole
tetrahydro
oxo
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PCT/IB2001/002729
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French (fr)
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WO2002055519A2 (en
Inventor
Donald Eugene Butler
Randall Lee Dejong
Jade Douglas Nelson
Michael Gerard Pamment
Timothy Lee Stuk
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Warner-Lambert Company Llc
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Priority to BR0116739-1A priority Critical patent/BR0116739A/en
Application filed by Warner-Lambert Company Llc filed Critical Warner-Lambert Company Llc
Priority to MXPA03005284A priority patent/MXPA03005284A/en
Priority to CA002432064A priority patent/CA2432064C/en
Priority to EP01273081A priority patent/EP1353917B1/en
Priority to HU0302647A priority patent/HUP0302647A3/en
Priority to DE60127583T priority patent/DE60127583T2/en
Priority to PL01365283A priority patent/PL365283A1/en
Priority to IL15646101A priority patent/IL156461A0/en
Priority to AU2002222430A priority patent/AU2002222430B8/en
Priority to KR1020037009159A priority patent/KR100582326B1/en
Priority to JP2002556188A priority patent/JP4190285B2/en
Priority to DK01273081T priority patent/DK1353917T3/en
Publication of WO2002055519A2 publication Critical patent/WO2002055519A2/en
Publication of WO2002055519A3 publication Critical patent/WO2002055519A3/en
Priority to HK04103610A priority patent/HK1060572A1/en
Priority to CY20071100653T priority patent/CY1106590T1/en
Priority to IL189359A priority patent/IL189359A0/en
Priority to IL189357A priority patent/IL189357A0/en
Priority to IL189358A priority patent/IL189358A0/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)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Diabetes (AREA)
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  • General Chemical & Material Sciences (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • 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)
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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 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.
PCT/IB2001/002729 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 WO2002055519A2 (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
IL15646101A IL156461A0 (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
MXPA03005284A MXPA03005284A (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.
CA002432064A CA2432064C (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
EP01273081A EP1353917B1 (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
HU0302647A HUP0302647A3 (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 and their intermediates
DE60127583T DE60127583T2 (en) 2001-01-09 2001-12-27 NEW METHOD OF SYNTHESIS OF N-PHENYL-5- (4-FLUORPHENYL) -1- (2 - ((2R, 4R) -4-HYDROXY-6-OXOTETRAHYDROPYRAN-2-YL) ETHYL) -2-ISOPROPYL-4- PHENYL-1H-pyrrole-3-carboxamide
KR1020037009159A KR100582326B1 (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
AU2002222430A AU2002222430B8 (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-phenyl-1H-pyrrole-3-carboxylic acid phenylamide
PL01365283A PL365283A1 (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
BR0116739-1A BR0116739A (en) 2001-01-09 2001-12-27 Process for Synthesis of 5- (4-Fluorophenyl) -1- [2 - ((2r, 4r) -4-hydroxy-6-oxo-tetrahydro-pyran-2-yl) -ethyl] -2- isopropyl-4-phenyl1h-pyrrol-3-carb oxylic
JP2002556188A JP4190285B2 (en) 2001-01-09 2001-12-27 5- (4-Fluorophenyl) -1- [2-((2R, 4R) -4-hydroxy-6-oxotetrahydropyran-2-yl) ethyl] -2-isopropyl-4-phenyl-1H-pyrrole- Novel process for the synthesis of 3-carboxylic acid phenylamides
DK01273081T DK1353917T3 (en) 2001-01-09 2001-12-27 New 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
HK04103610A HK1060572A1 (en) 2001-01-09 2004-05-21 Preparation process of pyrrole-3-carboxylic acid phenylamide derivatices.
CY20071100653T CY1106590T1 (en) 2001-01-09 2007-05-14 NEW 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 PHENYLAMIDIC
IL189357A IL189357A0 (en) 2001-01-09 2008-02-07 Novel compounds
IL189359A IL189359A0 (en) 2001-01-09 2008-02-07 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
IL189358A IL189358A0 (en) 2001-01-09 2008-02-07 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 (2)

Application Number Priority Date Filing Date Title
US26050501P 2001-01-09 2001-01-09
US60/260,505 2001-01-09

Publications (2)

Publication Number Publication Date
WO2002055519A2 WO2002055519A2 (en) 2002-07-18
WO2002055519A3 true WO2002055519A3 (en) 2002-09-19

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Application Number Title Priority Date Filing Date
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

Country Status (25)

Country Link
US (7) US6476235B2 (en)
EP (1) EP1353917B1 (en)
JP (2) JP4190285B2 (en)
KR (3) KR100582326B1 (en)
CN (4) CN1907984A (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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