WO2006131782A1 - Procede de preparation de methyl-2-(3-(2-(7-chloro-2-quinolinyl-ethenyl)-phenyl)-3-oxopropyl)benzoate - Google Patents

Procede de preparation de methyl-2-(3-(2-(7-chloro-2-quinolinyl-ethenyl)-phenyl)-3-oxopropyl)benzoate Download PDF

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Publication number
WO2006131782A1
WO2006131782A1 PCT/IB2005/002705 IB2005002705W WO2006131782A1 WO 2006131782 A1 WO2006131782 A1 WO 2006131782A1 IB 2005002705 W IB2005002705 W IB 2005002705W WO 2006131782 A1 WO2006131782 A1 WO 2006131782A1
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WO
WIPO (PCT)
Prior art keywords
formula
methyl
palladium
quinolinyl
chloro
Prior art date
Application number
PCT/IB2005/002705
Other languages
English (en)
Inventor
Sandip Jayant Parekh
Harmander Pal Singh Chawla
Anil Shankar Chowdhary
Ajay Mangubhai Patel
Original Assignee
Glade Organics Private Limited
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 Glade Organics Private Limited filed Critical Glade Organics Private Limited
Publication of WO2006131782A1 publication Critical patent/WO2006131782A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/18—Halogen atoms or nitro radicals

Definitions

  • the invention relates to an improved process for the manufacture of Methyl-2-(3-(2-(7- chloro-2-quinolinyl)-ethenyl)phenyl)-3-oxopropyl)benzoate II, which is an intermediate in the manufacture of Montelukast sodium of formula I.
  • the compound of the formula I is well known as a Leukotriene antagonist and an inhibitor of leukotriene biosynthesis. These compounds are effective in the treatment of asthmatic disorders, etc. Several processes for the manufacture of the same are reported.
  • An important intermediate in the synthesis of the compound of the formula I is the compound of the formula II. This intermediate is synthesized by subjecting intermediate of formula III to conditions of Heck reaction as known to those well versed in the art. This transformation involves coupling of the olefin III with the aryl halide of formula IV, followed by prototropic shifts to give the title compound II.
  • the European Patent No. 480717 relates to the manufacture of unsaturated hydroxyalkylquinoline acids having activity as leukotriene antagonists and to methods for their preparation. Also reported are the compounds of the formula II, which is as stated above an important intermediate in the synthesis of compounds of the formula I. This intermediate is manufactured from a compound of the formula III by utilizing Lithium salts, Palladium acetate and methyl-2-bromoacetate.
  • European Patent No. 500360 relates to quinoline-containing ketoacids as leukotriene antagonists and to methods for their preparation. Also, reported are the compounds of the formula II, which is as stated above an important intermediate in the synthesis of compounds of the formula I. This intermediate is manufactured by utilizing Lithium salts, Palladium acetate and methyl 2-bromoacetate. This process again suffers from low yields and is hence not economical. Therefore it is very difficult and inconvenient to carry out the process.
  • European Patent No. 399818 relates to diarylstyrylquinoline diacids as leukotriene antagonists and to methods for their preparation. Also reported are the compounds of the formula II, which is as stated above an important intermediate in the synthesis of compounds of the formula I. This intermediate is manufactured by utilizing Lithium salts, Palladium acetate and methyl 2-bromoacetate. This process gives the compound of the formula II in low purity and yields (c.a 65-75%) and is not commercially viable. Thus, there is a need in the art to provide a process for the manufacture of compound of formula II in high yield and purity.
  • An object of the present invention is to provide a process for the transformation from a compound of the formula III to a compound of the formula II in high yields and purity.
  • the present invention relates to a process for the preparation of methyl 2-(3-(2-(7-chloro-2- quinolinyl)-ethenyl)phenyl)-3-oxopropyl)benzoate of the formula II,
  • R 1 , R 2 , R3 and R 4 connote alkyl such as methyl, ethyl, n- or iso-propyl, n-, iso- or tert- butyl etc; aralkyl such as benzyl, phenethyl, substituted phenethyl, phenylpropyl etc; aryl such as phenyl, substituted phenyl etc and X could be halo, alkyl sulfonate etc.
  • the ionic liquid used in the synthesis may be selected from the group comprising tetrabutyl ammonium bromide, tetrabutyl ammonium chloride, tetrabutyl ammonium hydrogen sulfate, or imidazolium salts such as l-bromo-3- methylimidazolium hexaphosphate or l-bromo3-methylimidazolium tetrafluoroborate, 1- cyclohexyl-3 -methyl tris(perfluoroethyl)trifluorophosphate or quaternary phoshphonium salts such as tetraphenylphosphonium bromide or methyltriphenylphosphonium bromide, preferably tetrabutyl ammonium bromide.
  • a favorable ratio of the ionic liquid with respect to the substrate of formula III may be 10-50% but preferably 25-30%.
  • the ionic liquid along with the catalyst may be recycled a number of
  • One advantage of the invention is that it does not require use of any additional conventional solvent like dimethylformamide (DMF) or N-methylpyrrolidone (NMP). Further the final product may be isolated by extraction and distillation and the catalyst residue recycled several times. This also results in reduced environmental burden since there is practically no discharge. Since, the present invention utilizes ionic liquids for conversion of a compound of formula III to a compound of formula II, the efficiency of the process is better, the product quality is also better and ecologically beneficial.
  • DMF dimethylformamide
  • NMP N-methylpyrrolidone
  • the metal catalyst may be selected from the group comprising palladium acetate, palladium chloride, palladium bromide or palladium complex with triaryl phosphine.
  • the preferred catalyst is palladium acetate.
  • the amount of catalyst may be in a weight ratio of 0.1 to 1.0 % with respect to compound III.
  • the base employed is selected from group comprising of triethyl amine, triisopropyl amine or tributyl amine, preferably triethyl amine.
  • the base is preferably used in the range of 1.0 to 5.0 moles with respect to the input substrate of formula III.
  • the organic solvent comprises of a hydrocarbon such as benzene, toluene, preferably toluene or a chlorinated hydrocarbon such as methylene chloride, ethylene chloride, alkyl nitriles such as acetonitriles.
  • a hydrocarbon such as benzene, toluene, preferably toluene or a chlorinated hydrocarbon such as methylene chloride, ethylene chloride, alkyl nitriles such as acetonitriles.
  • the above example can be repeated up to a maximum of 5 batches without affecting the yield and quality parameters.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Quinoline Compounds (AREA)

Abstract

L'invention concerne un procédé de préparation de méthyl-2-(3-(2-(7-chloro-2-quinolinyl)-éthényl)phényl)-3-oxopropyl)benzoate de formule II avec un rendement et une pureté élevées.
PCT/IB2005/002705 2005-06-07 2005-09-08 Procede de preparation de methyl-2-(3-(2-(7-chloro-2-quinolinyl-ethenyl)-phenyl)-3-oxopropyl)benzoate WO2006131782A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN680MU2005 2005-06-07
IN680/MUM/2005 2005-06-07

Publications (1)

Publication Number Publication Date
WO2006131782A1 true WO2006131782A1 (fr) 2006-12-14

Family

ID=37498159

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2005/002705 WO2006131782A1 (fr) 2005-06-07 2005-09-08 Procede de preparation de methyl-2-(3-(2-(7-chloro-2-quinolinyl-ethenyl)-phenyl)-3-oxopropyl)benzoate

Country Status (1)

Country Link
WO (1) WO2006131782A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0480717A1 (fr) * 1990-10-12 1992-04-15 Merck Frosst Canada Inc. Acides hydroxyalkylquinoliniques insaturés comme antagonistes de leukotriène
EP0500360A1 (fr) * 1991-02-21 1992-08-26 Merck Frosst Canada Inc. Des céto-acides contenant une quinoléine comme antagonistes des leukotriènes

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0480717A1 (fr) * 1990-10-12 1992-04-15 Merck Frosst Canada Inc. Acides hydroxyalkylquinoliniques insaturés comme antagonistes de leukotriène
EP0500360A1 (fr) * 1991-02-21 1992-08-26 Merck Frosst Canada Inc. Des céto-acides contenant une quinoléine comme antagonistes des leukotriènes

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KING A.O. ET AL.: "An efficient synthesis of LTD4 Antagonist L-699,392", JOURNAL OF ORGANIC CHEMISTRY, vol. 58, 1993, pages 3731 - 3735, XP002358965 *
MO J. ET AL.: "Ionic liquid promoted, highly regioselective Heck arylation of electron-rich olefins by aryl halides", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 127, 2005, pages 751 - 760, XP002391313 *

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