EP1360179A2 - Method for preparing compounds derived from thiazolidinedione, oxazolidinedione or hydantoin - Google Patents

Method for preparing compounds derived from thiazolidinedione, oxazolidinedione or hydantoin

Info

Publication number
EP1360179A2
EP1360179A2 EP02704834A EP02704834A EP1360179A2 EP 1360179 A2 EP1360179 A2 EP 1360179A2 EP 02704834 A EP02704834 A EP 02704834A EP 02704834 A EP02704834 A EP 02704834A EP 1360179 A2 EP1360179 A2 EP 1360179A2
Authority
EP
European Patent Office
Prior art keywords
pph
formula
compound
formic acid
transition metal
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.)
Withdrawn
Application number
EP02704834A
Other languages
German (de)
French (fr)
Inventor
Michel Bulliard
Yvon Derrien
Tony Pintus
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.)
Zach System SA
Original Assignee
PPG Sipsy SAS
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
Priority claimed from FR0102010A external-priority patent/FR2820741A1/en
Application filed by PPG Sipsy SAS filed Critical PPG Sipsy SAS
Publication of EP1360179A2 publication Critical patent/EP1360179A2/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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
    • C07D263/44—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings 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
    • C07D233/72—Two oxygen atoms, e.g. hydantoin
    • C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
    • C07D233/78—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/96—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
    • C07D277/34—Oxygen atoms
    • 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 compounds derived from thiazolidinedione, oxazolidinedione or hydantoin of formula (I) from the following compounds of formula (II):
  • - Q represents an oxygen atom, a sulfur atom
  • - Ql represents an oxygen atom or a sulfur atom
  • Ri and R2 identical or different, represent a hydrogen atom, a C ⁇ o alkyl chain; cycloalkyl, alkylaryl, arylalkyl; said alkyl, cycloalkyl, alkylaryl or arylalkyl groups being optionally substituted by an alkyl, an alkoxy or aryloxy, a halogen, a hydroxy, a sulfino, a sulfonyl, an amino such as NH 2 , NHR 3 , N (R 3 ) 2 , with R3 representing an alkyl, an alkoxy or an alkylcarbonyl.
  • the compounds derived from thiazolidinedione, oxazolidinedione or hydantoin of formula (I) are known as synthetic intermediates for the preparation of pharmaceutical active ingredients or as pharmaceutical active ingredients such as, for example, pioglitazone, rosiglitazone , troglitazone, ciglitazone.
  • the process according to the invention has the advantages of preparing said compounds of formula (I) by generating few impurities, of obtaining a total conversion rate, of eliminating the use of large quantity of solvent, of being selective and easily isolate the product of formula (I).
  • the method according to the present invention therefore makes it possible to reduce the financial costs of industrial production of the compounds of formula (I).
  • a subject of the present invention is therefore a process for the preparation of a compound derived from thiazolidinedione, oxazolidinedione or hydantoin of formula (I) from a compound of formula (II) below:
  • the catalyst based on transition metal used either in the hydrogen transfer reaction or in the hydrogenation reaction, is chosen from a homogeneous or heterogeneous catalyst.
  • transition metal catalysts said to be heterogeneous, supported or not, mention is made of Pt, Pt / C, Pt (0) 2 , Pd, Pd / C, Pd / CaC0 3 , Pd / Si0 2 , Pd / BaC0 3 , Pd (OH) 2 / C, Ir, Ir / C, Ru, Ru / C, Rh, Raney Ni, Fe.
  • a secondary solvent is advantageously chosen from water, a hydrocarbon such as hexane, heptane, octane, nonane, decane, benzene, toluene and xylene, an ether such as tetrahydrofuran, dioxane , dimethoxyethane, diisopropyl ether and diethylene glycol dimethyl ether, an ester such as ethyl acetate, butyl acetate and ethyl propionate, a ketone such as acetone, diisopropyl ketone, methylisobutyl ketone, ethyl ethyl ketone and acetyl acetone, an alcohol such as methanol, ethanol, n-propanol, isopropanol, butanol, isobutanol, and meth
  • a preferred form of implementation of the process for the preparation of compounds of formula (I) by a hydrogenation reaction according to the invention comprises the treatment of the compound of formula (II), in the presence of formic acid and a catalyst, under the following operating conditions:
  • a preferred form of implementation of the process for the preparation of compounds of formula (I) by a hydrogen transfer reaction according to the invention comprises the treatment of the compound of formula (II), in the presence of formic acid and d 'A catalyst, preferably under the following operating conditions:
  • reaction time of between 0.5 and 40 hours.
  • Example 1 Preparation of the compound; [(ethyl-5-pyridyl-2-) ethoxy-4-] benzyl ⁇ -5-thiazolidine-2,4-dione-2,4 according to a hydrogenation reaction.
  • reaction medium is cooled to room temperature (20-25 ° C).
  • the catalyst is filtered and rinsed with 60 ml of formic acid.
  • the filtrate is concentrated under vacuum at 40 ° C to 40 ml. 80 ml of water and 60 ml of formic acid are added to the concentrate. The pH value of the solution is equal to 0.93. 101 g of a solution of
  • the crude product is washed in ethanol as follows.
  • the product is dissolved in 172 ml of ethanol, the mixture is refluxed for 30 min, cooled to 10 ° C and the product is filtered.
  • Example 2 Preparation of the compound; ⁇ [(ethyl-5-pyridyl-2-) ethoxy-4-1benzyl> -5-thiazolidine-2, 4-dione-2, 4 according to a hydrogen transfer reaction by homogeneous catalysis.
  • Example 3 Compound preparation; ⁇ [(ethyl-5-pyridyl-2-) ethoxy-4-lbenzyl> -5-thiazolidine-2,4-dione-2,4 according to a hydrogen transfer reaction by heterogeneous catalysis.
  • the solution is heated to reflux for 5 hours.
  • the HPLC profile of the reaction medium indicates a transformation rate of 78%.
  • the medium is concentrated to 5 ml.
  • Example 4 Compound preparation; -f [(ethyl-5-pyridyl-2-) ethoxy-4-1benzyl> -5-thiazolidine-2,4-dione-2,4 according to a hydrogen transfer reaction by heterogeneous catalysis.
  • the solution is heated to reflux (105 ° C) for 21 hours.
  • the HPLC profile of the reaction medium indicates a conversion rate of 66%.
  • the medium is concentrated to 5 ml.
  • Example 5 Preparation of the compound: -ff (ethyl-5-pyridyl-2-) ethoxy-4-] benzyl> -5-thiazolidine-2, 4-dione-2, 4 according to a hydrogen transfer reaction by heterogeneous catalysis. Under nitrogen, in a 0.5 1 flask are introduced 20 g of ⁇ [(ethyl-5-pyridyl-2-) ethoxy-4-] benzylylidene ⁇ -5-thiazolidine-2, 4-dione-2, 4, 0.6 g of Pt (0) 2 (2.5% platinum / substrate) and 200 ml of 99% formic acid. The solution is heated to the temperature of 84
  • the HPLC profile of the reaction medium indicates a conversion rate of 98.3% into the product formed.
  • reaction medium is filtered and the filtrate is concentrated to 40 ml.
  • the product is filtered.
  • the product is purified by repasting in ethanol.
  • the solution is heated to the temperature of 80-85 ° C for 19 hours 30 minutes.
  • the HPLC profile of the reaction medium indicates a conversion rate of 98.4% into the product formed.
  • Example 7 Preparation of the compound: -f [(ethyl-5-pyridyl-2-) ethoxy-4-1benzyl> -5-thiazolidine-2,4-dione-2,4 according to a hydrogen transfer reaction by heterogeneous catalysis. Under nitrogen, in a 100 ml tetracol are introduced 5 g of ⁇ [(ethyl-5-pyridyl-2-) ethoxy-4-] benzylylidene ⁇ -5-thiazolidine-2, 4-dione-2, 4, 0.203 g of Pt (0) 2 (3.4% platinum / substrate) and 50 ml of 99% formic acid. The solution is heated to the temperature of 80-
  • the HPLC profile of the reaction medium indicates a conversion rate of 98% into the product formed.

Landscapes

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

Abstract

The invention relates to method for preparing a compound derived from thiazolidinedione, oxazolidinedione or hydantoin having formula (I) from a compound having formula (II) as follows: wherein Q represents an oxygen atom, a sulphur atom, Q1 represents an oxygen atom or a sulphur atom, R1 and R2, which can be identical or different, represent a hydrogen atom, a C1-10 alkyl chain; a cycloalkyl, an alkylaryl, arylalkyl; said alkyl, cycloakyl, alkylaryl or arylalkyl groups being optionally substituted by an alkyl, an alkoxy or aryloxy, a halogen, a hydroxy, a sulfino, a sulfonyl, an amino such as NH2, NHR3, N(R3)2, with R3 representing an alkyl, an alkoxy or an alkylcarbonyl. The inventive method is characterised in that a compound having formula (II) is made to react with the formic acid in the presence of a transition metal-based catalyst in order to produce the corresponding formula (I) compound.

Description

PROCEDE DE PREPARATION DE COMPOSES DERIVES DE THIAZOLIDINEDIONE, D 'OXAZOLIDINEDIONE OU D'HYDANTOINE. PROCESS FOR THE PREPARATION OF COMPOUNDS DERIVED FROM THIAZOLIDINEDIONE, OXAZOLIDINEDIONE OR HYDANTOIN.
La présente invention concerne un nouveau procédé de préparation de composés dérivés de thiazolidinedione, d'oxazolidinedione ou d'hydantoine de formule (I) à partir de composés de formule (II) suivantes :The present invention relates to a new process for the preparation of compounds derived from thiazolidinedione, oxazolidinedione or hydantoin of formula (I) from the following compounds of formula (II):
Dans lesquellesIn which
- Q représente un atome d'oxygène, un atome de soufre;- Q represents an oxygen atom, a sulfur atom;
- Ql représente un atome d'oxygène ou un atome de soufre- Ql represents an oxygen atom or a sulfur atom
Ri et R2 , identiques ou différents, représentent un atome d'hydrogène, une chaîne alkyle en C^o ; un cycloalkyle, un alkylaryle, un arylalkyle ; lesdits groupements alkyles, cycloalkyle, alkylaryle ou arylalkyle étant éventuellement substitués par un alkyle, un alkoxy ou aryloxy, un halogène, un hydroxy, un sulfino, un sulfonyle, un amino tel que NH2, NHR3, N(R3)2, avec R3 représentant un alkyle, un alkoxy ou un alkylcarbonyle.Ri and R2, identical or different, represent a hydrogen atom, a C ^ o alkyl chain; cycloalkyl, alkylaryl, arylalkyl; said alkyl, cycloalkyl, alkylaryl or arylalkyl groups being optionally substituted by an alkyl, an alkoxy or aryloxy, a halogen, a hydroxy, a sulfino, a sulfonyl, an amino such as NH 2 , NHR 3 , N (R 3 ) 2 , with R3 representing an alkyl, an alkoxy or an alkylcarbonyl.
Les composés dérivés de thiazolidinedione, d'oxazolidinedione ou d'hydantoine de formule (I) sont connus en tant qu'intermédiaires de synthèse pour la préparation de principes actifs pharmaceutiques ou en tant que principes actifs pharmaceutiques comme par exemple, la pioglitazone, la rosiglitazone , la troglitazone , la ciglitazone. On connaît de l'art antérieur, des procédés de préparation de composés dérivés de thiazolidinedione, d'oxazolidinedione ou d'hydantoines : - via une réduction en présence d'hydrure de métaux comme décrit dans la demande de brevet internationale WO 9837073, ouThe compounds derived from thiazolidinedione, oxazolidinedione or hydantoin of formula (I) are known as synthetic intermediates for the preparation of pharmaceutical active ingredients or as pharmaceutical active ingredients such as, for example, pioglitazone, rosiglitazone , troglitazone, ciglitazone. Are known from the prior art, methods for preparing compounds derived from thiazolidinedione, oxazolidinedione or hydantoines: - via a reduction in the presence of metal hydride as described in international patent application WO 9837073, or
- via une réduction en présence de métaux de transition comme décrit dans le brevet européen EP 257781, - ou encore via une réduction en présence de magnésium et de methanol comme décrit dans la demande de brevet internationale WO 9837073.- via a reduction in the presence of transition metals as described in European patent EP 257781, - or also via a reduction in the presence of magnesium and methanol as described in the international patent application WO 9837073.
Ces divers procédés présentent les inconvénients de générer de grandes quantités d'impuretés qui peuvent être supérieures à 10 % comme pour la synthèse de la pioglitazone, d'utiliser d'une grande quantité de catalyseur ou de solvant, d'avoir des problèmes de sélectivité, d'isolement du composé formé de formule (I).These various processes have the drawbacks of generating large amounts of impurities which can be greater than 10% as for the synthesis of pioglitazone, of using a large amount of catalyst or of solvent, of having selectivity problems , isolation of the compound formed of formula (I).
Le procédé selon l'invention présente les avantages de préparer lesdits composés de formule (I) en générant peu d'impuretés, d'obtenir un taux de transformation total, d'éliminer l'utilisation de grande quantité de solvant, d'être sélectif et d'isoler facilement le produit de formule (I). Le procédé selon la présente invention permet donc de diminuer les coûts financiers de production industrielle des composés de formule (I).The process according to the invention has the advantages of preparing said compounds of formula (I) by generating few impurities, of obtaining a total conversion rate, of eliminating the use of large quantity of solvent, of being selective and easily isolate the product of formula (I). The method according to the present invention therefore makes it possible to reduce the financial costs of industrial production of the compounds of formula (I).
La présente invention a donc pour objet, un procédé de préparation d'un composé dérivé de thiazolidinedione, d'oxazolidinedione ou d'hydantoine de formule (I) à partir d'un composé de formule (II) suivante : A subject of the present invention is therefore a process for the preparation of a compound derived from thiazolidinedione, oxazolidinedione or hydantoin of formula (I) from a compound of formula (II) below:
( M ) ( D dans lesquelles Q, Ql, RI et R2 ont les mêmes significations que précédemment, caractérisé en ce que l'on fait réagir un composé de formule (II) avec de l'acide formique, soit comme donneur d'hydrogène dans une réaction dite de transfert d'hydrogène, soit comme solvant dans une réaction d'hydrogénation, en présence d'un catalyseur à base d'un métal de transition, pour obtenir le composé de formule (I) correspondant. L'acide formique utilisé peut-être de l'acide formique à 100%, ou une solution comprenant de l'acide formique, dont la teneur en acide formique varie de 0,1 à 99 %, pour autant que la dite solution puisse dissoudre le composé de formule (II). Ladite solution peut être une solution aqueuse ou une solution organique ou un mélange de celles-ci.(M) (D in which Q, Ql, RI and R2 have the same meanings as above, characterized in that a compound of formula (II) is reacted with formic acid, either as a hydrogen donor in a so-called hydrogen transfer reaction, either as a solvent in a hydrogenation reaction, in the presence of a catalyst based on a transition metal, to obtain the corresponding compound of formula (I). perhaps using 100% formic acid, or a solution comprising formic acid, the formic acid content of which varies from 0.1 to 99%, provided that said solution can dissolve the compound of formula (II). Said solution can be an aqueous solution or an organic solution or a mixture of these.
Avantageusement, le catalyseur à base de métal de transition, mis en œuvre soit dans la réaction de transfert d'hydrogène soit dans la réaction d'hydrogénation, est choisi parmi un catalyseur homogène ou hétérogène .Advantageously, the catalyst based on transition metal, used either in the hydrogen transfer reaction or in the hydrogenation reaction, is chosen from a homogeneous or heterogeneous catalyst.
Parmi les catalyseurs à base de métal de transition dits homogènes, on cite Ir(C0D)Cl, Ru(p- cymène)Cl2, Ru(COD)Cl2, Ru(PPh3) 3C12, RuCl3, Ru(PPh3)4Cl, RuCl3.3H20, Ru(PPh3)4H2, Rh(PPh3)3Cl, RhCl3.3H20, Ru(PPh3)4H, Rh(COD) trifluorornéthanesuifonate, (C6H12)3P(COD)pyridine- Ir(F)5, Ir(PPh3)3H2Cl, Ir(PPh3)3HCl2, Ir(PPh3)2H3, Ir(PPh3)3H5, Ir(PPh3)2(CO)X [X≈Cl, Br,I], Ir (PPh3) 2 (CO) H, Os (PPh3)3HCl, Pd(OAc)2,PdCl2, Pd(PPh3)2Cl2, Pd(NH4)2Cl4, Pt (PPh3 ) 2C12 , PtCl4K2, Fe(PPh3)2Cl2, Ni(PBu-Ω3)2, ReCl5. Parmi les catalyseurs à base de métal de transition dits hétérogènes, supporté ou non, on cite Pt, Pt/C, Pt(0)2, Pd, Pd/C, Pd/CaC03, Pd/Si02, Pd/BaC03, Pd(OH)2/C, Ir, Ir/C, Ru, Ru/C, Rh, Ni de Raney, Fe.Among the so-called homogeneous transition metal catalysts, mention is made of Ir (C0D) Cl, Ru (p- cymene) Cl 2 , Ru (COD) Cl 2 , Ru (PPh 3 ) 3 C1 2 , RuCl 3 , Ru ( PPh 3 ) 4 Cl, RuCl 3 .3H 2 0, Ru (PPh 3 ) 4 H 2 , Rh (PPh 3 ) 3 Cl, RhCl 3 .3H 2 0, Ru (PPh 3 ) 4 H, Rh (COD) trifluorornethanesulfonate , (C 6 H 12 ) 3 P (COD) pyridine- Ir (F) 5 , Ir (PPh 3 ) 3 H 2 Cl, Ir (PPh 3 ) 3 HCl 2 , Ir (PPh 3 ) 2 H 3 , Ir ( PPh 3 ) 3 H 5 , Ir (PPh 3 ) 2 (CO) X [X≈Cl, Br, I], Ir (PPh 3 ) 2 (CO) H, Os (PPh 3 ) 3 HCl, Pd (OAc) 2 , PdCl 2 , Pd (PPh 3 ) 2 Cl 2 , Pd (NH 4 ) 2 Cl 4 , Pt (PPh 3 ) 2 C1 2 , PtCl 4 K 2 , Fe (PPh 3 ) 2 Cl 2 , Ni (PBu- Ω 3 ) 2 , ReCl 5 . Among the transition metal catalysts said to be heterogeneous, supported or not, mention is made of Pt, Pt / C, Pt (0) 2 , Pd, Pd / C, Pd / CaC0 3 , Pd / Si0 2 , Pd / BaC0 3 , Pd (OH) 2 / C, Ir, Ir / C, Ru, Ru / C, Rh, Raney Ni, Fe.
Le procédé selon l'invention peut être réalisé en présence ou non d'un solvant secondaire. Un tel solvant secondaire est avantageusement choisi parmi l'eau, un hydrocarbure comme l'hexane, l'heptane, l'octane, le nonane, le décane, le benzène, le toluène et le xylène, un éther comme le tétrahydrofurane, le dioxane, le diméthoxyéthane , le diisopropyl éther et le diéthylène glycol diméthyl éther, un ester comme l'acétate d'éthyle, l'acétate de butyle et le propionate d'éthyle, une cétone comme l'acétone, le diisopropy lcétone , le méthylisobutylcétone , le éthyléthylcétone et l'acétylacétone, un alcool comme le methanol, l'éthanol, le n-propanol, l'iso-propanol, le butanol, l'isobutanol, et le méthoxyéthanol , un halogénure d' alkyle comme le dic lorométhane, le chloroforme et le 1,2-dichloroéthane, un acide comme l'acide acétique, l'acide propionique, l'acide butanoique, un amide comme le diméthylformamide, un suif oxyde comme le diméthylsulf oxyde.The process according to the invention can be carried out in the presence or not of a secondary solvent. Such a secondary solvent is advantageously chosen from water, a hydrocarbon such as hexane, heptane, octane, nonane, decane, benzene, toluene and xylene, an ether such as tetrahydrofuran, dioxane , dimethoxyethane, diisopropyl ether and diethylene glycol dimethyl ether, an ester such as ethyl acetate, butyl acetate and ethyl propionate, a ketone such as acetone, diisopropyl ketone, methylisobutyl ketone, ethyl ethyl ketone and acetyl acetone, an alcohol such as methanol, ethanol, n-propanol, isopropanol, butanol, isobutanol, and methoxyethanol, an alkyl halide such as dicoromethane, chloroform and 1,2-dichloroethane, an acid such as acetic acid, propionic acid, butanoic acid, an amide such as dimethylformamide, a tallow oxide such as dimethylsulfoxide.
Une forme préférée de mise en œuvre du procédé de préparation de composés de formule (I) par une réaction d'hydrogénation selon l'invention, comprend le traitement du composé de formule (II), en présence d'acide formique et d'un catalyseur, dans les conditions opératoires suivantes :A preferred form of implementation of the process for the preparation of compounds of formula (I) by a hydrogenation reaction according to the invention comprises the treatment of the compound of formula (II), in the presence of formic acid and a catalyst, under the following operating conditions:
- la présence ou non d'un solvant secondaire, tel que défini précédemment ;- the presence or absence of a secondary solvent, as defined above;
- une température comprise entre 0 et +150 °C- a temperature between 0 and +150 ° C
- un rapport quantité de métal / quantité de substrat compris entre 1/10000 et 5 % ; - une pression d'hydrogène entre 0,1 et 50 bars ;- a quantity of metal / quantity of substrate ratio of between 1/10000 and 5%; - a hydrogen pressure between 0.1 and 50 bars;
- une durée de réaction comprise entre 0,5 et- a reaction time of between 0.5 and
40 heures,40 hours,
Une forme préférée de mise en œuvre du procédé de préparation de composés de formule (I) par une réaction de transfert d'hydrogène selon l'invention, comprend le traitement du composé de formule (II), en présence d'acide formique et d'un catalyseur, dans les conditions opératoires préférentiellement les suivantes :A preferred form of implementation of the process for the preparation of compounds of formula (I) by a hydrogen transfer reaction according to the invention, comprises the treatment of the compound of formula (II), in the presence of formic acid and d 'A catalyst, preferably under the following operating conditions:
- la présence ou non d'un solvant secondaire, tel que défini précédemment ;- the presence or absence of a secondary solvent, as defined above;
- une température comprise entre 0 et +150 °C ; - un rapport quantité de métal / quantité de substrat compris entre 1/10000 et 5 /100 ;- a temperature between 0 and +150 ° C; - a quantity of metal / quantity of substrate ratio of between 1/10000 and 5/100;
- une durée de réaction comprise entre 0,5 et 40 heures.- a reaction time of between 0.5 and 40 hours.
D'autres avantages et caractéristiques de l'invention apparaîtront des exemples qui suivent donnés à titre d'illustration du procédé de préparation de composés de formule (I) à partir de composés de formule (II). Les composés de formule (II) constituant les substrats de la réaction peuvent être préparés par tout procédé de l'art antérieur connu de la littérature.Other advantages and characteristics of the invention will appear from the examples which follow, given by way of illustration of the process for the preparation of compounds of formula (I) from compounds of formula (II). The compounds of formula (II) constituting the substrates of the reaction can be prepared by any method of the prior art known from the literature.
Exemple 1 : Préparation du composé ; [(éthyl- 5-pyridyl-2-)éthoxy-4-]benzyl}-5-thiazolidine-2,4-dione-2,4 selon une réaction d'hydrogénation.Example 1: Preparation of the compound; [(ethyl-5-pyridyl-2-) ethoxy-4-] benzyl} -5-thiazolidine-2,4-dione-2,4 according to a hydrogenation reaction.
Dans un Buchi de 0,5 1 sont introduits 20 g de { [ (éthyl-5-pyridyl-2-)éthoxy-4-]benzylylidene}-5- thiazolidine-2,4-dione-2,4, 10 g de Pd/C à 10 % et 200 ml d'acide formique à 95-97 %. On purge à l'azote puis à l'hydrogène. Sous une pression d'hydrogène de 8 bars, on chauffe à 75-80 °C pendant 6 heures.Into a 0.5 l Buchi are introduced 20 g of {[(ethyl-5-pyridyl-2-) ethoxy-4-] benzylylidene} -5- thiazolidine-2,4-dione-2,4, 10 g of Pd / C at 10% and 200 ml of 95-97% formic acid. It is purged with nitrogen and then with hydrogen. Under a hydrogen pressure of 8 bars, it is heated to 75-80 ° C for 6 hours.
Le milieu réactionnel est refroidi à la température ambiante (20-25 °C). On filtre le catalyseur que l'on rince avec 60 ml d'acide formique.The reaction medium is cooled to room temperature (20-25 ° C). The catalyst is filtered and rinsed with 60 ml of formic acid.
Le filtrat est concentré sous vide à 40 °C jusqu'à 40 ml. On ajoute sur le concentrât, 80 ml d'eau et 60 ml d'acide formique. La valeur du pH de la solution est égale à 0,93. On ajoute à ce milieu 101 g d'une solution deThe filtrate is concentrated under vacuum at 40 ° C to 40 ml. 80 ml of water and 60 ml of formic acid are added to the concentrate. The pH value of the solution is equal to 0.93. 101 g of a solution of
NaOH à 30 % jusqu'à une valeur du pH égale à 3,25, "on agite le milieu pendant 10 mn à 20 °C, et on filtre le produit.NaOH at 30% up to a pH value equal to 3.25, " the medium is stirred for 10 min at 20 ° C., and the product is filtered.
Le produit brut est lavé dans de l'éthanol comme suit. On met le produit en solution dans 172 ml d'éthanol, on chauffe au reflux pendant 30 mn, on refroidit à 10 °C et on filtre le produit.The crude product is washed in ethanol as follows. The product is dissolved in 172 ml of ethanol, the mixture is refluxed for 30 min, cooled to 10 ° C and the product is filtered.
Après séchage sous vide à 50 °C, on obtient 19,1 g de produit blanc. Rdt: 97,4 %.After drying under vacuum at 50 ° C., 19.1 g of white product are obtained. YId: 97.4%.
Exemple 2 : Préparation du composé ; {[(éthyl- 5-pyridyl-2-)éthoxy-4-1benzyl>-5-thiazolidine-2 ,4-dione-2 ,4 selon une réaction de transfert d'hydrogène par catalyse homogène .Example 2: Preparation of the compound; {[(ethyl-5-pyridyl-2-) ethoxy-4-1benzyl> -5-thiazolidine-2, 4-dione-2, 4 according to a hydrogen transfer reaction by homogeneous catalysis.
Sous azote, dans un ballon de 50 ml sont introduits 1 g de { [ ( éthyl-5-ρyridyl-2- ) éthoxy-4- ]benzylylidène}-5-thiazolidine-2 , 4-dione-2 , 4 , 61 mg de chloro-l,5-COD Iridium et 10 ml d'acide formique à 97 %. On chauffe la solution orangée aux reflux pendant 6 heures .Under nitrogen, into a 50 ml flask are introduced 1 g of {[(ethyl-5-ρyridyl-2-) ethoxy-4-] benzylylidene} -5-thiazolidine-2, 4-dione-2, 4, 61 mg of chloro-1,5-COD Iridium and 10 ml of 97% formic acid. The orange solution is heated to reflux for 6 hours.
A partir du milieu réactionnel, le profil HPLC indique un taux de transformation de 97 %. On concentre le milieu à 2 ml. On ajoute 9 ml d'eau et on filtre le produit. Exemple 3 ; Préparation du composé ; {[(éthyl- 5-pyridyl-2-)éthoxy-4-lbenzyl>-5-thiazolidine-2,4-dione-2,4 selon une réaction de transfert d'hydrogène par catalyse hétérogène .From the reaction medium, the HPLC profile indicates a conversion rate of 97%. The medium is concentrated to 2 ml. 9 ml of water are added and the product is filtered. Example 3; Compound preparation; {[(ethyl-5-pyridyl-2-) ethoxy-4-lbenzyl> -5-thiazolidine-2,4-dione-2,4 according to a hydrogen transfer reaction by heterogeneous catalysis.
Sous azote, dans un ballon de 50 ml sont introduits 2,5 g de { [ (éthyl-5-pyridyl-2- ) éthoxy-4-2.5 g of {[(ethyl-5-pyridyl-2-) ethoxy-4- are introduced into a 50 ml flask
]benzylylidène}-5-thiazolidine-2,4-dione-2,4, 3 g de Rh/C à 5 % humide à 57,8% (2,5 % de rhodium métal/substrat)et 10 ml d'acide formique à 99 %.] benzylylidene} -5-thiazolidine-2,4-dione-2,4, 3 g Rh / C at 5% wet at 57.8% (2.5% rhodium metal / substrate) and 10 ml of acid 99% formic.
On chauffe la solution aux reflux pendant 5 heures .The solution is heated to reflux for 5 hours.
Le profil HPLC du milieu réactionnel indique un taux de transformation de 78 %.The HPLC profile of the reaction medium indicates a transformation rate of 78%.
On concentre le milieu à 5 ml.The medium is concentrated to 5 ml.
On ajoute 9 ml d'eau et on filtre le produit.9 ml of water are added and the product is filtered.
Exemple 4 ; Préparation du composé ; -f[(éthyl- 5-pyridyl-2-)éthoxy-4-1benzyl>-5-thiazolidine-2,4-dione-2,4 selon une réaction de transfert d'hydrogène par catalyse hétérogène .Example 4; Compound preparation; -f [(ethyl-5-pyridyl-2-) ethoxy-4-1benzyl> -5-thiazolidine-2,4-dione-2,4 according to a hydrogen transfer reaction by heterogeneous catalysis.
Sous azote, dans un ballon de 50 ml sont introduits 2,5 g de { [ (éthyl-5-pyridyl-2- )éthoxy-4- ]benzylylidène}-5-thiazolidine-2 ,4-dione-2 , 4, 1,37 g de2.5 g of {[(ethyl-5-pyridyl-2-) ethoxy-4-] benzylylidene} -5-thiazolidine-2, 4-dione-2, 4, are introduced into nitrogen in a 50 ml flask. 1.37 g of
Pd/C à 10 % humide à 53,2% (2,5 % de palladium métal/substrat)et 10 ml d'acide formique à 99 %.Pd / C at 10% wet at 53.2% (2.5% palladium metal / substrate) and 10 ml of 99% formic acid.
On chauffe la solution aux reflux (105 °C) pendant 21 heures. Le profil HPLC du milieu réactionnel indique un taux de transformation de 66 %.The solution is heated to reflux (105 ° C) for 21 hours. The HPLC profile of the reaction medium indicates a conversion rate of 66%.
On concentre le milieu à 5 ml.The medium is concentrated to 5 ml.
On ajoute 19 ml d'eau et on filtre le produit. Exemple 5 ; Préparation du composé : -ff(éthyl- 5-pyridyl-2- )éthoxy-4-]benzyl>-5-thiazolidine-2 , 4-dione-2 , 4 selon une réaction de transfert d'hydrogène par catalyse hétérogène . Sous azote, dans un ballon de 0,5 1 sont introduits 20 g de { [ ( éthyl-5-pyridyl-2- ) éthoxy-4- ]benzylylidène}-5-thiazolidine-2 , 4-dione-2 , 4, 0,6 g de Pt(0)2 (2,5 % de platine/substrat )et 200 ml d'acide formique à 99 %. On chauffe la solution à la température de 8419 ml of water are added and the product is filtered. Example 5; Preparation of the compound: -ff (ethyl-5-pyridyl-2-) ethoxy-4-] benzyl> -5-thiazolidine-2, 4-dione-2, 4 according to a hydrogen transfer reaction by heterogeneous catalysis. Under nitrogen, in a 0.5 1 flask are introduced 20 g of {[(ethyl-5-pyridyl-2-) ethoxy-4-] benzylylidene} -5-thiazolidine-2, 4-dione-2, 4, 0.6 g of Pt (0) 2 (2.5% platinum / substrate) and 200 ml of 99% formic acid. The solution is heated to the temperature of 84
°C pendant 19 heures 30 mn.° C for 19 hours 30 min.
Le profil HPLC du milieu réactionnel indique un taux de transformation de 98,3 % en produit formé.The HPLC profile of the reaction medium indicates a conversion rate of 98.3% into the product formed.
On filtre le milieu réactionnel et on concentre le filtrat à 40 ml.The reaction medium is filtered and the filtrate is concentrated to 40 ml.
On ajoute 140 ml d'eau et on ajuste le pH à 3,2 par addition de soude à 30%.140 ml of water are added and the pH is adjusted to 3.2 by adding 30% sodium hydroxide.
On filtre le produit.The product is filtered.
Le produit est purifié par réempâtage dans de l'éthanol.The product is purified by repasting in ethanol.
Après séchage sous vide à 50 °C, on isole 19,7 g de produit.After drying under vacuum at 50 ° C., 19.7 g of product are isolated.
Rdt : 96,5 %YId: 96.5%
Exemple 6 : Préparation du composé : {[(éthyl-Example 6: Preparation of the compound: {[(ethyl-
5-pyridyl-2- )éthoxy-4- 1benzyl}-5-thiazolidine-2 , 4-dione-2 , 4 selon une réaction de transfert d'hydrogène par catalyse hétérogène . • • 5-pyridyl-2-) ethoxy-4-1benzyl} -5-thiazolidine-2, 4-dione-2, 4 according to a hydrogen transfer reaction by heterogeneous catalysis. • •
Sous azote, dans un tétracol de 100 ml sont introduits 5 g de { [ ( éthyl-5-pyridyl-2- ) éthoxy-4- ]benzylylidène}-5-thiazolidine-2,4-dione-2,4, 0,148 g de Pt(0)2 (2,5 % de platine/substrat)et 35 ml d'acide formique à 99 %.Under nitrogen, in a 100 ml tetracol are introduced 5 g of {[(ethyl-5-pyridyl-2-) ethoxy-4-] benzylylidene} -5-thiazolidine-2,4-dione-2,4, 0.148 g Pt (0) 2 (2.5% platinum / substrate) and 35 ml of 99% formic acid.
On chauffe la solution à la température de 80- 85 °C pendant 19 heures 30 mn. Le profil HPLC du milieu réactionnel indique un taux de transformation de 98,4 % en produit formé.The solution is heated to the temperature of 80-85 ° C for 19 hours 30 minutes. The HPLC profile of the reaction medium indicates a conversion rate of 98.4% into the product formed.
On isole le produit comme précédemment avec un rendement de 96,5 % .The product is isolated as above with a yield of 96.5%.
Exemple 7 ; Préparation du composé : -f[(éthyl- 5-pyridyl-2-)éthoxy-4-1benzyl>-5-thiazolidine-2,4-dione-2,4 selon une réaction de transfert d'hydrogène par catalyse hétérogène . Sous azote, dans un tétracol de 100 ml sont introduits 5 g de { [ ( éthyl-5-pyridyl-2- ) ëthoxy-4- ]benzylylidène}-5-thiazolidine-2, 4-dione-2, 4, 0,203 g de Pt(0)2 (3,4 % de platine/substrat) et 50 ml d'acide formique à 99 % . On chauffe la solution à la température de 80-Example 7; Preparation of the compound: -f [(ethyl-5-pyridyl-2-) ethoxy-4-1benzyl> -5-thiazolidine-2,4-dione-2,4 according to a hydrogen transfer reaction by heterogeneous catalysis. Under nitrogen, in a 100 ml tetracol are introduced 5 g of {[(ethyl-5-pyridyl-2-) ethoxy-4-] benzylylidene} -5-thiazolidine-2, 4-dione-2, 4, 0.203 g of Pt (0) 2 (3.4% platinum / substrate) and 50 ml of 99% formic acid. The solution is heated to the temperature of 80-
85 °C pendant 16 heures.85 ° C for 16 hours.
Le profil HPLC du milieu réactionnel indique un taux de transformation de 98 % en produit formé.The HPLC profile of the reaction medium indicates a conversion rate of 98% into the product formed.
On isole le produit comme précédemment avec un rendement de 94,5 %. The product is isolated as above with a yield of 94.5%.

Claims

REVENDICATIONS
1) Procédé de préparation d'un composé dérivé de thiazolidinedione, d'oxazolidinedione ou d'hydantoine de formule (I) à partir d'un composé de formule (II) suivante :1) Process for the preparation of a compound derived from thiazolidinedione, oxazolidinedione or hydantoin of formula (I) from a compound of formula (II) below:
( H ) ( I ) dans lesquelles(H) (I) in which
- Q représente un atome d' ' oxygène, un atome de soufre,- Q represents an oxygen atom, a sulfur atom,
- Ql représente un atome d'oxygène ou un atome de soufre,- Ql represents an oxygen atom or a sulfur atom,
Ri et R2 , identiques ou différents, représentent un atome d'hydrogène, une chaîne alkyle en Cj.n, ; un cycloalkyle, un alkylaryle, un arylalkyle ; lesdits groupements alkyles, cycloalkyle, alkylaryle ou arylalkyle étant éventuellement substitués par un alkyle, un alkoxy ou aryloxy, un halogène, un hydroxy, un sulfino, un sulfonyle, un amino tel que NH2, NHR3, N(R3)2, avec R3 représentant un alkyle, un alkoxy ou un alkylcarbonyle, caractérisé en ce que l'on fait réagir un composé de formule (II) avec de l'acide formique, soit comme donneur d'hydrogène dans une réaction dite de transfert d'hydrogène, soit comme solvant dans une réaction d'hydrogénation, en présence d'un catalyseur à base d'un métal de transition, pour obtenir le composé de formule (I) correspondant. 2) Procédé selon la revendication 1, caractérisé en ce que l'acide formique est de l'acide formique à 100% ou une solution comprenant de l'acide formique dont la teneur en acide formique varie de 0,1 à 99 %, ladite solution pouvant être une solution aqueuse ou une solution organique ou un mélange de celles-ci.Ri and R2, identical or different, represent a hydrogen atom, a C j alkyl chain. n ,; cycloalkyl, alkylaryl, arylalkyl; said alkyl, cycloalkyl, alkylaryl or arylalkyl groups being optionally substituted by an alkyl, an alkoxy or aryloxy, a halogen, a hydroxy, a sulfino, a sulfonyl, an amino such as NH 2 , NHR 3 , N (R 3 ) 2 , with R3 representing an alkyl, an alkoxy or an alkylcarbonyl, characterized in that a compound of formula (II) is reacted with formic acid, either as a hydrogen donor in a so-called hydrogen transfer reaction , or as a solvent in a hydrogenation reaction, in the presence of a catalyst based on a transition metal, to obtain the corresponding compound of formula (I). 2) Method according to claim 1, characterized in that the formic acid is 100% formic acid or a solution comprising formic acid whose formic acid content varies from 0.1 to 99%, said solution may be an aqueous solution or an organic solution or a mixture of these.
3) Procédé selon l'une des revendications 1 ou 2, caractérisé en ce le catalyseur à base de métal de transition est un catalyseur homogène ou hétérogène.3) Method according to one of claims 1 or 2, characterized in that the catalyst based on transition metal is a homogeneous or heterogeneous catalyst.
4) Procédé selon la revendication 3, caractérisé en ce que le catalyseur homogène à base de métal de transition est choisi parmi Ir(C0D)Cl, Ru(p- cymène)Cl2, Ru(COD)Cl2, Ru(PPh3 ) 3C12 , RuCl3, Ru(PPh3)4Cl, RuCl3.3H20, Ru(PPh3)4H2, Rh(PPh3)3Cl, RhCl3.3H20, Ru(PPh3)4H, Rh(COD) trifluorométhanesulfonate, (C6H12)3P(COD)pyridine- Ir(F)6, Ir(PPh3)3H2Cl, Ir(PPh3) 3HC12, Ir(PPh3)2H3, Ir(PPh3)3H5, Ir(PPh3)2(CO)X [X=C1, Br,I], Ir (PPh3) 2 (CO)H, Os (PPh3)3HCl, Pd(OAc )2,PdCl2, Pd(PPh3 ) 2C12 , Pd(NH4)2Cl4, Pt (PPh3 ) 2C12 , PtCl4K2, Fe(PPh3)2Cl2, Ni (PBu-n3)2, ReCl5.4) Process according to claim 3, characterized in that the homogeneous catalyst based on transition metal is chosen from Ir (C0D) Cl, Ru (p- cymene) Cl 2 , Ru (COD) Cl 2 , Ru (PPh 3 ) 3 C1 2 , RuCl 3 , Ru (PPh 3 ) 4 Cl, RuCl 3 .3H 2 0, Ru (PPh 3 ) 4 H 2 , Rh (PPh 3 ) 3 Cl, RhCl 3 .3H 2 0, Ru (PPh 3 ) 4 H, Rh (COD) trifluoromethanesulfonate, (C 6 H 12 ) 3 P (COD) pyridine- Ir (F) 6 , Ir (PPh 3 ) 3 H 2 Cl, Ir (PPh 3 ) 3 HC1 2 , Ir (PPh 3 ) 2 H 3 , Ir (PPh 3 ) 3 H 5 , Ir (PPh 3 ) 2 (CO) X [X = C1, Br, I], Ir (PPh 3 ) 2 (CO) H, Os ( PPh 3 ) 3 HCl, Pd (OAc) 2 , PdCl 2 , Pd (PPh 3 ) 2 C1 2 , Pd (NH 4 ) 2 Cl 4 , Pt (PPh 3 ) 2 C1 2 , PtCl 4 K 2 , Fe (PPh 3 ) 2 Cl 2 , Ni (PBu-n 3 ) 2 , ReCl 5 .
5) Procédé selon la revendication 3, caractérisé en ce que le catalyseur hétérogène à base de métal de transition est choisi parmi Pt, Pt/C, Pt(0)2, Pd, Pd/C, Pd/CaC03, Pd/Si02, Pd/BaC03, Pd(OH)2/C, Ir, Ir/C, Ru, Ru/C, Rh, Ni de Raney, Fe.5) Process according to claim 3, characterized in that the heterogeneous catalyst based on transition metal is chosen from Pt, Pt / C, Pt (0) 2 , Pd, Pd / C, Pd / CaC0 3 , Pd / Si0 2 , Pd / BaC0 3 , Pd (OH) 2 / C, Ir, Ir / C, Ru, Ru / C, Rh, Raney Ni, Fe.
6) Procédé selon l'une quelconque des revendications précédentes, caractérisé en ce que l'on fait réagir un composé de formule (II) avec de l'acide formique, en présence d'un catalyseur à base d'un métal de transition et en présence d'un solvant secondaire. 7) Procédé selon la revendication 6, caractérisé en ce que le solvant secondaire est choisi parmi l'eau, un hydrocarbure comme l'hexane, l'heptane, l'octane, le nonane, le décane, le benzène, le toluène et le xylène, un éther comme le tétrahydrofurane, le dioxane, le diméthoxyéthane , le diisopropyl éther et le diéthylène glycol diméthyl éther, un ester comme l'acétate d'éthyle, l'acétate de butyle et le propionate d'éthyle, une cétone comme l'acétone, le diisopropy lcétone , le méthylisobutylcétone , le méthyléthylcétone et l'acétylacétone, un alcool comme le methanol, l'éthanol, le n-propanol, l'iso-propanol, le butanol, l'isobutanol, et le méthoxyéthanol, un halogénure d' alkyle comme le dichlorométhane, le chloroforme et le 1,2-dichloroéthane, un acide comme l'acide acétique, l'acide propionique, l'acide butanoique, un amide comme le diméthylformamide, un suif oxyde comme le diméthylsulf oxyde.6) Process according to any one of the preceding claims, characterized in that a compound of formula (II) is reacted with formic acid, in the presence of a catalyst based on a transition metal and in the presence of a secondary solvent. 7) Process according to claim 6, characterized in that the secondary solvent is chosen from water, a hydrocarbon such as hexane, heptane, octane, nonane, decane, benzene, toluene and xylene, an ether like tetrahydrofuran, dioxane, dimethoxyethane, diisopropyl ether and diethylene glycol dimethyl ether, an ester like ethyl acetate, butyl acetate and ethyl propionate, a ketone like l acetone, diisopropy ketone, methylisobutyl ketone, methyl ethyl ketone and acetylacetone, an alcohol such as methanol, ethanol, n-propanol, isopropanol, butanol, isobutanol, and methoxyethanol alkyl halide such as dichloromethane, chloroform and 1,2-dichloroethane, an acid such as acetic acid, propionic acid, butanoic acid, an amide such as dimethylformamide, a tallow oxide such as dimethylsulfoxide.
8) Procédé selon l'une quelconque des revendications 1 à 7, caractérisé en ce que l'on fait réagir un composé de formule (II) avec de l'acide formique comme solvant dans une réaction d'hydrogénation en présence d'hydrogène, et en présence d'un catalyseur à base d'un métal de transition, dans les conditions opératoires suivantes :8) Process according to any one of claims 1 to 7, characterized in that a compound of formula (II) is reacted with formic acid as solvent in a hydrogenation reaction in the presence of hydrogen, and in the presence of a catalyst based on a transition metal, under the following operating conditions:
- en présence ou non d'un solvant secondaire ;- in the presence or absence of a secondary solvent;
- une température comprise entre 0 et +150 °C- a temperature between 0 and +150 ° C
- un rapport quantité de métal / quantité de substrat compris entre 1/10000 et 5 % ; - une pression d'hydrogène entre 0,1 et 50 bars ;- a quantity of metal / quantity of substrate ratio of between 1/10000 and 5%; - a hydrogen pressure between 0.1 and 50 bars;
- une durée de réaction comprise entre 0,5 et 40 heures. 9) Procédé selon l'une quelconque des revendications 1 à 7, caractérisé en ce que l'on fait réagir un composé de formule (II) avec de l'acide formique comme donneur d'hydrogène dans une réaction dite de transfert d'hydrogène, en présence d'un catalyseur à base d'un métal de transition, dans les conditions opératoires suivantes :- a reaction time of between 0.5 and 40 hours. 9) Method according to any one of claims 1 to 7, characterized in that a compound of formula (II) is reacted with formic acid as hydrogen donor in a reaction called hydrogen transfer , in the presence of a catalyst based on a transition metal, under the following operating conditions:
- en présence ou non d'un solvant secondaire, tel que défini précédemment ; - une température comprise entre 0 et +150 °C ;- in the presence or not of a secondary solvent, as defined above; - a temperature between 0 and +150 ° C;
- un rapport quantité de métal / quantité de substrat compris entre 1/10000 et 5 /100 ;- a quantity of metal / quantity of substrate ratio of between 1/10000 and 5/100;
- une durée de réaction comprise entre 0,5 et 40 heures. - a reaction time of between 0.5 and 40 hours.
EP02704834A 2001-02-14 2002-02-14 Method for preparing compounds derived from thiazolidinedione, oxazolidinedione or hydantoin Withdrawn EP1360179A2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
FR0102010A FR2820741A1 (en) 2001-02-14 2001-02-14 Pure 5-alkyl-thiazolidinedione, oxazolidinedione or hydantoin derivative preparation, for use as drug or intermediate, by reduction of corresponding alkylidene compound using formic acid
FR0102010 2001-02-14
FR0105206 2001-04-17
FR0105206A FR2820742B1 (en) 2001-02-14 2001-04-17 PROCESS FOR THE PREPARATION OF COMPOUNDS DERIVED FROM THIAZOLIDINEDIONE, OXAZOLIDINEDIONE OR HYDANTOIN
PCT/FR2002/000571 WO2002064577A2 (en) 2001-02-14 2002-02-14 Method for preparing compounds derived from thiazolidinedione, oxazolidinedione

Publications (1)

Publication Number Publication Date
EP1360179A2 true EP1360179A2 (en) 2003-11-12

Family

ID=26212876

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02704834A Withdrawn EP1360179A2 (en) 2001-02-14 2002-02-14 Method for preparing compounds derived from thiazolidinedione, oxazolidinedione or hydantoin

Country Status (13)

Country Link
US (1) US6849741B2 (en)
EP (1) EP1360179A2 (en)
JP (1) JP2004520401A (en)
KR (1) KR100856140B1 (en)
CN (1) CN1491218A (en)
AU (1) AU2002238645A1 (en)
BR (1) BR0206967A (en)
CA (1) CA2438105A1 (en)
FR (1) FR2820742B1 (en)
IL (1) IL157101A0 (en)
MX (1) MXPA03007263A (en)
RU (1) RU2003127720A (en)
WO (1) WO2002064577A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003053367A2 (en) * 2001-12-20 2003-07-03 Teva Pharmaceutical Industries Ltd. Hydrogenation of precursors to thiazolidinedione antihyperglycemics
CZ297347B6 (en) * 2004-09-21 2006-11-15 Zentiva, A. S. Process for preparing rosiglitazone
EP1903042A3 (en) * 2006-09-22 2008-05-28 Cadila Pharmaceuticals Limited An improved process for hydrogenation of 5-(substituted Benzylidene) 2,4- Thiazolidine Dione compounds to give corresponding ( +/- ) 5- (substituted Benzyl ) 2,4-Thiazolidine Dione

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812570A (en) * 1986-07-24 1989-03-14 Takeda Chemical Industries, Ltd. Method for producing thiazolidinedione derivatives
EP0839812A1 (en) * 1990-04-27 1998-05-06 Sankyo Company Limited Preparation of benzylthiazolidine derivatives
AU3231093A (en) * 1991-12-20 1993-07-28 Upjohn Company, The A reduction method for substituted 5-methylene-thiazolidinediones
JP3163361B2 (en) * 1992-03-12 2001-05-08 味の素株式会社 Method for producing 5-alkylhydantoin derivative
US5399632A (en) * 1992-09-30 1995-03-21 Exxon Research & Engineering Co. Hydrogenation process for unsaturated homo and copolymers
JPH06199808A (en) * 1993-01-04 1994-07-19 Ajinomoto Co Inc Production of 5-cyclohexylmethylhydantoin derivative and intermediate for production thereof
JPH08277279A (en) * 1995-04-05 1996-10-22 Nitto Chem Ind Co Ltd Production of benzylthiazolidindione derivative
US5952509A (en) * 1996-06-27 1999-09-14 Takeda Chemical Industries, Ltd. Production of benzaldehyde compounds
UY24886A1 (en) * 1997-02-18 2001-08-27 Smithkline Beecham Plc TIAZOLIDINDIONA
DE19711616A1 (en) * 1997-03-20 1998-09-24 Boehringer Mannheim Gmbh Improved process for the preparation of thiazolidinediones
JP4084501B2 (en) * 1999-07-01 2008-04-30 三井化学株式会社 α-Mercaptocarboxylic acid and process for producing the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO02064577A2 *

Also Published As

Publication number Publication date
AU2002238645A1 (en) 2002-08-28
KR20030082594A (en) 2003-10-22
FR2820742A1 (en) 2002-08-16
US20040059121A1 (en) 2004-03-25
CN1491218A (en) 2004-04-21
IL157101A0 (en) 2004-02-08
CA2438105A1 (en) 2002-08-22
BR0206967A (en) 2004-03-09
WO2002064577A2 (en) 2002-08-22
WO2002064577A3 (en) 2003-01-03
JP2004520401A (en) 2004-07-08
US6849741B2 (en) 2005-02-01
KR100856140B1 (en) 2008-09-03
FR2820742B1 (en) 2005-03-11
RU2003127720A (en) 2005-03-20
MXPA03007263A (en) 2005-02-14

Similar Documents

Publication Publication Date Title
CN1926102B (en) Process for preparing N-protected 4-ketoproline derivatives
EP2042497B1 (en) Method for producing strontium ranelate and its hydrates
EP1907396B1 (en) Method for preparing 4 -amino-4'-demethyl-4-desoxypodophyllotoxin
CH679150A5 (en)
EP1360179A2 (en) Method for preparing compounds derived from thiazolidinedione, oxazolidinedione or hydantoin
JPS6045621B2 (en) Method for producing butanone derivatives
JPH10509177A (en) Method for producing 5-hydroxymethylthiazole
EP0069002A1 (en) Process for the preparation of (thienyl-2)-2 ethyl amines and (thienyl-3)-2 ethyl amines
FR2820741A1 (en) Pure 5-alkyl-thiazolidinedione, oxazolidinedione or hydantoin derivative preparation, for use as drug or intermediate, by reduction of corresponding alkylidene compound using formic acid
WO2008135386A1 (en) Chiral ligands of the n-heterocyclic carbene type for asymmetrical catalysis
JP3870647B2 (en) Process for producing optically active α-hydroxy ketones
CA1312625C (en) Process for the preparation of aromatic aldehydes
WO1996038447A1 (en) 2-azabicyclo[2.2.1]heptane derivatives, preparation and application thereof
EP0452168A1 (en) Process for the preparation of N-phenyl benzoquinone-imine
FR2686876A1 (en) PROCESS FOR THE PREPARATION OF ARYLACETIC ACIDS AND THEIR SALTS OF ALKALI METALS.
CH643226A5 (en) PROCESS FOR THE MANUFACTURE OF CARBONYL COMPOUNDS BY OXIDATION OF OLEFINIC COMPOUNDS.
EP0931059B1 (en) Method for preparing a cyanobiphenyl
WO2005030719A1 (en) Novel method for preparing cis-octahydro-isoindole
EP0828740B1 (en) 2-azabicyclo[2.2.1]heptane derivatives, preparation and application thereof
FR2947263A1 (en) PROCESS FOR CATALYZING HYDROGEN TRANSFER REACTIONS
WO2005030718A1 (en) Novel method of preparing cis-octahydro-isoindole
FR2687668A1 (en) Process for the preparation of alkylaromatic diamines, new diimines and diamines and use of the diamines obtained for the manufacture of polyamides
WO1999040060A1 (en) Method for hydrogenating 5-nitrosalicylic acids
FR2642426A1 (en) ORGANOGERMANIUM COMPOUND, PROCESSES FOR THEIR MANUFACTURE, AND INHIBITOR AGENT OF OPIOID PEPTIDE DEGRADATION ENZYMES
WO1999006392A1 (en) Method for preparing 2h-1 benzopyranes and synthesis intermediates

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20030822

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

17Q First examination report despatched

Effective date: 20040305

RIN1 Information on inventor provided before grant (corrected)

Inventor name: PINTUS, TONY

Inventor name: DERRIEN, YVON

Inventor name: BULLIARD, MICHEL,SYNKEM FOURNIER PHARMA

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20090901