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WO1997043283A1 - Nouveau procede pour preparer de la troglitazone - Google Patents

Nouveau procede pour preparer de la troglitazone Download PDF

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Publication number
WO1997043283A1
WO1997043283A1 PCT/EP1997/002519 EP9702519W WO9743283A1 WO 1997043283 A1 WO1997043283 A1 WO 1997043283A1 EP 9702519 W EP9702519 W EP 9702519W WO 9743283 A1 WO9743283 A1 WO 9743283A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
general formula
formula
protective group
reduction
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP1997/002519
Other languages
German (de)
English (en)
Inventor
Hans-Peter Wolff
Ernst-Christian Witte
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Roche Diagnostics GmbH
Original Assignee
Boehringer Mannheim GmbH
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 Boehringer Mannheim GmbH filed Critical Boehringer Mannheim GmbH
Priority to AU30911/97A priority Critical patent/AU3091197A/en
Publication of WO1997043283A1 publication Critical patent/WO1997043283A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a new process for the preparation of troglitazones, the compound of the formula (I)
  • the compound of formula (I) is described in EP-139421 and known under the name TROGLITAZONE as an antidiabetic agent for the oral treatment of diabetes mellitus, especially in the case of type II or type IIb. But also in type I, the substance proves to be effective because according to more recent knowledge, it lowers the need for exogenous insulin. It also has a positive influence on elevated blood pressure values and brings about a reduction in the levels of T ⁇ glyce ⁇ d and cholesterol. It is therefore also suitable for the prophylaxis of atherosclerotic diseases. The substance is therefore a valuable substance Medicines for the treatment of diabetic metabolic diseases, the effectiveness of which has been demonstrated in numerous clinical studies
  • Patent EP-139421 describes a production process for the compound (I), according to which the compound of the formula (VIII)
  • the MOM protective group used is also introduced via condensation with chloromethyl methyl ether. This chloromethyl ether is classified as clearly carcinogenic and therefore requires special protective and monitoring measures when handling
  • the process according to the invention thus consists of a reaction sequence, which is characterized in that one first starts from a compound of the general formula (II)
  • R4 is a reductively stable protective group for phenolic OH.
  • protective groups are known for example from biotechnology, e.g. As benzyl or MOM, benzyl is preferred.
  • Compounds of the general formula II are reacted with a trifluoromethanesulfonylating agent, preferably trifluoromethanesulfonic acid anhydride or trifluoromethylsulfonyl chloride, to give a compound of the general formula (III)
  • the main advantage of the process according to the invention consists in the process step of the gentle reduction of compounds of the general formula (V) with magnesium or preferably activated aluminum to compounds of the general formula (VI), which is easy to carry out in high yields, by using the mild reducing agents, in particular when used of aluminum, can reduce sensitivity Protective groups R 4 are used and the contamination of the compounds (VI) by partial gradual reductions in the aromatic ring systems, such as those which take place, for example, in the long-term catalytic hydrogenations, are largely prevented
  • the reaction can also be carried out in aprotic, polar solvents which are miscible with small amounts of water, such as dioxane or tetrahydrofuran, with the addition of small amounts of water as a proton donor.
  • This variant is a particularly gentle method of reduction.
  • the reaction is carried out at room temperature or elevated temperature preferably carried out at 40 ° C.
  • the activation of the aluminum is preferably carried out by treatment with a dilute mercury salt solution
  • the extracts are dried and evaporated.
  • the residue is suspended in 500 ml of water, stirred for 2 hours and the precipitate is filtered off with suction.
  • the precipitate is mixed 1 part of isohexane and 1 part of ethyl acetate were dissolved and filtered with this mixture as eluans over a short column of silica gel (control of the eluate using a thin layer chromatogram).
  • the eluate is evaporated and the residue after streaking through n dried at 50 ° C in a circulating air dryer.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé économique pour préparer de la troglitazone (I) en utilisant un composé de la formule générale (III).
PCT/EP1997/002519 1996-05-16 1997-05-16 Nouveau procede pour preparer de la troglitazone Ceased WO1997043283A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU30911/97A AU3091197A (en) 1996-05-16 1997-05-16 New process for preparing troglitazone

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19619818 1996-05-16
DE19619818.6 1996-05-16

Publications (1)

Publication Number Publication Date
WO1997043283A1 true WO1997043283A1 (fr) 1997-11-20

Family

ID=7794510

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/002519 Ceased WO1997043283A1 (fr) 1996-05-16 1997-05-16 Nouveau procede pour preparer de la troglitazone

Country Status (2)

Country Link
AU (1) AU3091197A (fr)
WO (1) WO1997043283A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000076488A3 (fr) * 1999-06-14 2001-05-10 Smithkline Beecham Plc Nouveau traitement

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0139421A1 (fr) * 1983-08-30 1985-05-02 Sankyo Company Limited Dérivés de la thiazolidine, leur préparation et composition les contenant
EP0306228A1 (fr) * 1987-09-04 1989-03-08 Beecham Group Plc Thiazolidinediones substituées
EP0454501A2 (fr) * 1990-04-27 1991-10-30 Sankyo Company Limited Dérivés de benzylidène thiazolidines, leur préparation et leur utilisation pour l'inhibition de péroxydes lipidiques

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0139421A1 (fr) * 1983-08-30 1985-05-02 Sankyo Company Limited Dérivés de la thiazolidine, leur préparation et composition les contenant
EP0306228A1 (fr) * 1987-09-04 1989-03-08 Beecham Group Plc Thiazolidinediones substituées
EP0454501A2 (fr) * 1990-04-27 1991-10-30 Sankyo Company Limited Dérivés de benzylidène thiazolidines, leur préparation et leur utilisation pour l'inhibition de péroxydes lipidiques

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000076488A3 (fr) * 1999-06-14 2001-05-10 Smithkline Beecham Plc Nouveau traitement

Also Published As

Publication number Publication date
AU3091197A (en) 1997-12-05

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