[go: up one dir, main page]

WO2009104200A1 - A method for preparation of thiazolidinedione derivatives - Google Patents

A method for preparation of thiazolidinedione derivatives Download PDF

Info

Publication number
WO2009104200A1
WO2009104200A1 PCT/IN2008/000230 IN2008000230W WO2009104200A1 WO 2009104200 A1 WO2009104200 A1 WO 2009104200A1 IN 2008000230 W IN2008000230 W IN 2008000230W WO 2009104200 A1 WO2009104200 A1 WO 2009104200A1
Authority
WO
WIPO (PCT)
Prior art keywords
thiazolidinedione derivatives
water
preparation
acid
polyethylene glycol
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/IN2008/000230
Other languages
French (fr)
Other versions
WO2009104200A8 (en
Inventor
Sandhya Ujire
Manicka Ramamoorthy Sivakumar
Rekha Hiremath
Deepa Shanker Suvarna
Pullela Venkata Srinivas
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.)
Biocon Ltd
Original Assignee
Biocon Ltd
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 Biocon Ltd filed Critical Biocon Ltd
Publication of WO2009104200A1 publication Critical patent/WO2009104200A1/en
Publication of WO2009104200A8 publication Critical patent/WO2009104200A8/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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 discloses a new method of preparing organic compounds.
  • the present invention provides a new solvent system for reduction method to prepare few specific pharmaceutically active compounds in particular thiazolidinedione derivatives, including Pioglitazone, Rosiglitazone, Ciglitazone and E ⁇ glitazone. These compounds are known for the treatment of diabetes.
  • Thiazolidine derivatives are useful for the treatment of diabetes.
  • the effect on insulin resistance of thiazolidine derivatives are described, e.g. in, Chang, et al, Diabetes 32: 839-845 ( 1983) and Chang, et al, Diabetes 32:830-838 (1983).
  • the preparation of these thiazolidinedione derivatives includes the reduction of an intermediate previously performed by a troublesome high pressure hydrogenation using palladium on carbon or ra ⁇ ney nickel as catalyst. To avoid difficulties in hydrogenation, the need is an easy and efficient method of reduction.
  • D.A- Clark et al-. J- Med. Chem., 34:319-325 (1991 ) discloses the process for making substituted dihydrobenzopyran and dihydrobenzofuran thiazolidine-2,4-diones, using hydrogen on a palladium on carbon catalyst.
  • WO 93/13095, WO 04/007490 and WO 06/026934 disclose method of reduction for the antihyperglycemic Pioglitazone, Englitazone, Ciglitazone and Rosiglitazone. However, they do not disclose method of instant invention including the solvent used and its recovery enabling, it to be used for subsequent reduction reactions.
  • the present invention provides new and effective process for reducing thiazolidinedione derivatives.
  • the present invention particularly provides the use of a solvent during the reduction of thiazolidinedione derivatives which is easy to handle and having effective reaction timings. Interestingly, the recovery of the solvent after the reaction will reduce cost of the production. This method also helps in better effluent management.
  • the present method is economical and can be advantageously applied on an industrial scale.
  • the method yields thiazolidinedione derivatives in a quality needed for pharmaceutical substances.
  • the main object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives by reducing intermediates of thiazolidinedione derivatives having double bonds.
  • Still another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives which provides for recovery of the solvent that can be used for future reactions.
  • Still another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives by employing cheaper and easily available raw-materials.
  • Still another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives which reduces the cost of production and helps in better effluent management.
  • the bivalent metal is cobalt.
  • the alkaline solution is aqueous solution of sodium hydroxide.
  • the polyethylene glycol is polyethylene glycol-400 grade.
  • the pH is adjusted in the range between 4 to 6.5.
  • the acid is selected from a group comprising citric acid, tartaric acid, acetic acid or mixtures thereof.
  • the thiazolidinedione derivatives are selected from a group comprising pioglitazone, englitazone, ciglitazone and rosiglitazone.
  • the present invention provides a process for reducing thiazolidinedione derivatives like Pioglitazone, Englitazone, Ciglitazone and Rosiglitazone using cobalt ion, a ligand and a reducing agent. This process employs temperature in the range of 0-15 0 C and a suitable solvent which is mixture of solvents, viz. polyethylene glycol and water.
  • the method selected gives substantially pure product by using easily available solvent with a significant yield improvement.
  • the present method is economical and can be advantageously applied on an industrial scale.
  • the method yields thiazolidinedione derivatives in a quality needed for pharmaceutical substances
  • the present invention offers a reduction reaction in polyethylene glycol, which is more efficient because it is faster, easier and results in substantially improved yield of the desired product. It is also more convenient for scale up at plant, since no high-pressure hydrogenators are required. This also involves the recovery of the solvent which in turn reduces the cost of the production and better effluent management.
  • the present invention offers the reduction of thiazolidine derivatives which involves the reagents cobalt ion in the form of cobaltous chloride hexahydrate, the ligand dimethyl glyoxime in N, N dimethyl formamide, the reducing agent sodium borohydride and the solvent media for the reaction is polyethylene glycol.
  • Polyethylene glycol present in the mother liquor is used for future reactions without distillation or any other treatment for purification.
  • Reduction of thiazolidinedione derivative involves reacting thiazolidinedione derivative having double bond in a mixture of Polyethylene glycol-400 and water in the alkaline condition with metal ligand complex and a reducing agent at a controlled temperature ranging from 0 to 15°C.
  • Metal ion of metal ligand complex is selected from bivalent metals, preferably cobalt in the form of cobaltous chloride.
  • the said ligand is an aromatic or aliphatic ligand, preferably dimethyl glyoxime.
  • Reducing agents used are selected from Lithium borohydride, Potassium borohydride and Sodium borohydride. Suitable temperature conditions for the reduction are 0- 15 0 C.
  • Preferable temperature condition for the said reduction reaction for the addition of reagents is 0-5° C.
  • Preferred temperature condition for the reduction reaction is 10 to 15°C.
  • the reaction mixture is stirred for about 1 8 hrs and quenched by the addition of acetone at lower temperature, further reaction mass is neutralized by the addition of acetic acid.
  • the crystals are isolated by the addition of water and stirred at 10- 15 0 C followed by filtration and drying.
  • the mother liquor of the reaction mass can be taken as the solvent media by adjusting pH of the solution to 9-9.5 by aqueous solution of sodium hydroxide.
  • the recovery of the solvent polyethylene glycol reduces the cost of production and helps in better effluent management.
  • Acetone 160ml is added to the reaction mass after the completion of the reaction at 0- 5°C and stirred well and the pH of the reaction mass is adjusted to 6-6.5 using glacial acetic acid.
  • Water lit is added to the reaction mass and stirred at 10-15 0 C for 2hrs. The crystals formed are filtered followed by water wash and drying under high vacuum. Yield: 90%
  • Acetone 160ml is added to the reaction mass after the completion of the reaction at 0- 5 0 C and stirred well and the pH of the reaction mass is adjusted to 6-6.5 using glacial acetic acid. Water (l it) is added to the reaction mass and stirred at 10-15 0 C for 2hrs. The crystals formed are filtered followed by water wash and drying under high vacuum.
  • reaction mass is further cooled to 0-5 0 C and a solution of sodium borohydride (22.8g) and sodium hydroxide (0.46g) in water (140ml) is added at 0-5 0 C and stirred for 18 hrs.
  • Acetone 160ml is added to the reaction mass after the completion of the reaction at 0- 5°C and stirred well and the pH of the reaction mass is adjusted to 6-6.5 using glacial acetic acid.
  • Water (lit) is added to the reaction mass and stirred at 10-15 0 C for 2hrs. The crystals formed are Filtered followed by water wash and drying under high vacuum.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Manufacture Of Metal Powder And Suspensions Thereof (AREA)

Abstract

The present invention offers the conjugate reduction of α-β-unsaturated thiazolidinedione derivatives which involves the reagents cobalt ion in the form of cobaltous chloride hexahydrate, the ligand dimethyl glyoxime in N, N dimethyl formamide, the reducing agent sodium borohydride and the solvent media for the reaction is polyethylene glycol (PEG).

Description

A METHOD FOR PREPARATION OF THIAZOLIDINEDIONE
DERIVATIVES
FIELD OF THE INVENTION
The present invention discloses a new method of preparing organic compounds. In particular, the present invention provides a new solvent system for reduction method to prepare few specific pharmaceutically active compounds in particular thiazolidinedione derivatives, including Pioglitazone, Rosiglitazone, Ciglitazone and Eπglitazone. These compounds are known for the treatment of diabetes.
BACKGROUND AND PRIOR ART OF THE INVENTION Thiazolidine derivatives are useful for the treatment of diabetes. The effect on insulin resistance of thiazolidine derivatives are described, e.g. in, Chang, et al, Diabetes 32: 839-845 ( 1983) and Chang, et al, Diabetes 32:830-838 (1983). The preparation of these thiazolidinedione derivatives includes the reduction of an intermediate previously performed by a troublesome high pressure hydrogenation using palladium on carbon or raπney nickel as catalyst. To avoid difficulties in hydrogenation, the need is an easy and efficient method of reduction.
1391 82 (1988); Chem- Abstr., 109:6504h (1988); disclose the process for making thiazolidinedione derivatives, using hydrogen on a palladium on carbon catalyst.
D.A- Clark et al-. J- Med. Chem., 34:319-325 (1991 ) discloses the process for making substituted dihydrobenzopyran and dihydrobenzofuran thiazolidine-2,4-diones, using hydrogen on a palladium on carbon catalyst.
The preparation of these thiazolidinedione derivatives like Pioglitazone, Englitazone, Ciglitazone and Rosiglitazone includes the reduction of an intermediate previously performed by a troublesome high pressure hydrogenation on a palladium on carbon catalyst. Presently it is needed an easier, more efficient method for this reduction.
US 5,585.495 discuss the use of cobalt ion with a ligaπd and reducing agent for the new reduction method for making certain pharmaceutically active compounds, such as thiazolidinedione derivatives. The following references disclose cobalt catalyzed reductions: U. Leutenegger et a!.. Angew. C hem. InL Ed., 28:60 ( 1989) discloses the enantioselective reduction of α, β- unsaturated carboxylates with sodium borohydride and catalytic amounts of chiral cobalt semicorrin complexes; and M.N. Ricroch and A. Gaudemer, J- Organometal. Chem.. 67: 1 19 ( 1974) discloses (pyridinato) cobaloxiine, chloro (pyridinato) cobaloxime and vitamin B12 catalyzing the hydrogenalion of α, β-unsaturated esters by hydrogen or sodium borohydride. J. O. Oshy, et aL J.A.C.S. 108:67-72 (1986), discloses cobalt (Et)-mediated sodium borohydride and lithium aluminum hydride reductions, which do not involve the use of ligands.
WO 93/13095, WO 04/007490 and WO 06/026934 disclose method of reduction for the antihyperglycemic Pioglitazone, Englitazone, Ciglitazone and Rosiglitazone. However, they do not disclose method of instant invention including the solvent used and its recovery enabling, it to be used for subsequent reduction reactions.
The present invention provides new and effective process for reducing thiazolidinedione derivatives. The present invention particularly provides the use of a solvent during the reduction of thiazolidinedione derivatives which is easy to handle and having effective reaction timings. Interestingly, the recovery of the solvent after the reaction will reduce cost of the production. This method also helps in better effluent management.
The present method is economical and can be advantageously applied on an industrial scale. The method yields thiazolidinedione derivatives in a quality needed for pharmaceutical substances.
OBJECTS OF THE INVENTION
The main object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives by reducing intermediates of thiazolidinedione derivatives having double bonds.
Another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives at a temperature ranging between 0-250C. Yet another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives which is industrially viable and cost effective.
Still another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives which provides for recovery of the solvent that can be used for future reactions.
Still another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives by employing cheaper and easily available raw-materials.
Still another object of the present invention is to obtain a method for preparation of thiazolidinedione derivatives which reduces the cost of production and helps in better effluent management.
STATEMENT OF THE INVENTION
Accordingly, the present invention relates to a method for preparation of thiazolidinedione derivatives by reducing intermediates of thiazolidinedione derivatives having double bonds at temperature ranging between 0 to 25°C comprises, (a) adding sodium hydroxide solution into suspension of the intermediates of thiazolidinedione derivatives having double bonds in a mixture of polyethylene glycol and water; (b) adding metal ligand complex catalysts of bivalent metals in presence of at least one complexing agent; (c) adding sodium borohydride in alkaline solution and stirring; (d) adding acetone to quench the reaction; (e) adjusting pH with acid; (f) isolating crystals by addition of water; and (g) optionally re-using mother liquor as a solvent for future reduction reactions by basifying to pH values more than 9.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a method for preparation of thiazolidinedione derivatives by reducing intermediates of thiazolidinedione derivatives having double bonds at temperature ranging between 0 to 250C comprises, a. adding sodium hydroxide solution into suspension of the intermediates of thiazolidinedione derivatives having double bonds in a mixture of polyethylene glycol and water; b. adding metal ligand complex catalysts of bivalent metals in presence of at least one complexing agent; c. adding sodium borohydride in alkaline solution and stirring; d. adding acetone to quench the reaction; e. adjusting pH with acid; f. isolating crystals by addition of water; and g. optionally re-using mother liquor as a solvent for future reduction reactions by basifying to pH values more than 9.
In yet another embodiment of the present invention, the bivalent metal is cobalt.
In still another embodiment of the present invention, the alkaline solution is aqueous solution of sodium hydroxide.
In still another embodiment of the present invention, the polyethylene glycol is polyethylene glycol-400 grade.
In still another embodiment of the present invention, the pH is adjusted in the range between 4 to 6.5. In still another embodiment of the present invention, the acid is selected from a group comprising citric acid, tartaric acid, acetic acid or mixtures thereof.
In still another embodiment of the present invention, the thiazolidinedione derivatives are selected from a group comprising pioglitazone, englitazone, ciglitazone and rosiglitazone. The present invention provides a process for reducing thiazolidinedione derivatives like Pioglitazone, Englitazone, Ciglitazone and Rosiglitazone using cobalt ion, a ligand and a reducing agent. This process employs temperature in the range of 0-150C and a suitable solvent which is mixture of solvents, viz. polyethylene glycol and water.
Figure imgf000006_0001
PIOG LlTAZONE
Figure imgf000006_0002
ROSIGL1TAZONE
This process wherein the cobalt ion is in the form of cobaltous chloride hexahydrate, the ligand is dimethyl glyoxime in N, N dimethyl formamide and the reducing agent is sodium borohydride.
The method selected gives substantially pure product by using easily available solvent with a significant yield improvement.
The present method is economical and can be advantageously applied on an industrial scale. The method yields thiazolidinedione derivatives in a quality needed for pharmaceutical substances
The present invention offers a reduction reaction in polyethylene glycol, which is more efficient because it is faster, easier and results in substantially improved yield of the desired product. It is also more convenient for scale up at plant, since no high-pressure hydrogenators are required. This also involves the recovery of the solvent which in turn reduces the cost of the production and better effluent management.
The present invention offers the reduction of thiazolidine derivatives which involves the reagents cobalt ion in the form of cobaltous chloride hexahydrate, the ligand dimethyl glyoxime in N, N dimethyl formamide, the reducing agent sodium borohydride and the solvent media for the reaction is polyethylene glycol. Polyethylene glycol present in the mother liquor is used for future reactions without distillation or any other treatment for purification.
Reduction of thiazolidinedione derivative involves reacting thiazolidinedione derivative having double bond in a mixture of Polyethylene glycol-400 and water in the alkaline condition with metal ligand complex and a reducing agent at a controlled temperature ranging from 0 to 15°C. Metal ion of metal ligand complex is selected from bivalent metals, preferably cobalt in the form of cobaltous chloride. The said ligand is an aromatic or aliphatic ligand, preferably dimethyl glyoxime. Reducing agents used are selected from Lithium borohydride, Potassium borohydride and Sodium borohydride. Suitable temperature conditions for the reduction are 0- 150C. Preferable temperature condition for the said reduction reaction for the addition of reagents is 0-5° C. Preferred temperature condition for the reduction reaction is 10 to 15°C.The reaction mixture is stirred for about 1 8 hrs and quenched by the addition of acetone at lower temperature, further reaction mass is neutralized by the addition of acetic acid. The crystals are isolated by the addition of water and stirred at 10- 150C followed by filtration and drying.
For further reactions, the mother liquor of the reaction mass can be taken as the solvent media by adjusting pH of the solution to 9-9.5 by aqueous solution of sodium hydroxide. The recovery of the solvent polyethylene glycol reduces the cost of production and helps in better effluent management.
The invention is further elaborated with the help of following examples. However, these examples should not be construed to limit the scope of invention.
Example 1
Figure imgf000007_0001
Sodium hydroxide (9.26g) in water (160ml) is added to the suspension of N-(2-{4-[(E)- (2,4-dimethylidene-l,3-thiazolidin-5-ylidene)methyl]phenyl}ethyl)-N-methylpyridin-2- amine (10Og) in polyethylene glycol - 400 (500ml) and water (800ml) at 10-150C followed by the addition of cobaltous chloride hexahydrate (0.08g), Dimethyl glyoxime (1.39g) in N, N dimethyl formamide (30ml) at the same temperature. The reaction mass is further cooled to 0-50C and a solution of sodium borohydride (22.8g) and sodium hydroxide (0.46g) in water (140ml) is added at 0-50C and stirred for 18 hrs.
Acetone (160ml) is added to the reaction mass after the completion of the reaction at 0- 5°C and stirred well and the pH of the reaction mass is adjusted to 6-6.5 using glacial acetic acid. Water (lit) is added to the reaction mass and stirred at 10-150C for 2hrs. The crystals formed are filtered followed by water wash and drying under high vacuum. Yield: 90%
Example 2
DMG
Figure imgf000008_0001
Figure imgf000008_0002
PIOGLITAZONE
Sodium hydroxide (9.26g) in water (160ml) is added to the suspension of ((5£)-5-({4- [2-(5-ethylpyridin-2-yl)ethoxy)phenyl}methylidene)-l,3-thiazolidine-2,4-dione (10Og) in polyethylene glycol - 400 (500ml) and water (800ml) at 10-150C followed by the addition of cobaltous chloride hexahydrate (0.08g), Dimethyl glyoxime (1.39g) in N, N dimethyl formamide (30ml) at the same temperature. The reaction mass is further cooled to 0-50C and a solution of sodium borohydride (22.8g) and sodium hydroxide (0.46g) in water (140ml) is added at 0-50C and stirred for 18 hrs.
Acetone (160ml) is added to the reaction mass after the completion of the reaction at 0- 50C and stirred well and the pH of the reaction mass is adjusted to 6-6.5 using glacial acetic acid. Water (l it) is added to the reaction mass and stirred at 10-150C for 2hrs. The crystals formed are filtered followed by water wash and drying under high vacuum.
Yield: 88%
Example 3
Reuse of PEG- 400:
Figure imgf000009_0001
Suspension of N-(2-{4-[(£)-(2,4-dimethylidene-l,3-thiazolidin-5- ylidene)methyl]phenyl}ethyl)-N-methylpyridin-2-amine (10Og,) in the filtrate (after the crystallization of Rosiglitazone from example 1) containing PEG 400 ,water and acetic acid is basified to pH 9.0 to 9.5 using solution of sodium hydroxide in water at 10- 15°C. Cobaltous chloride hexahydrate (0.08g), Dimethyl glyoxime (1.39g) in Ν, Ν dimethyl formamide (30ml) are added at the same temperature. The reaction mass is further cooled to 0-50C and a solution of sodium borohydride (22.8g) and sodium hydroxide (0.46g) in water (140ml) is added at 0-50C and stirred for 18 hrs. Acetone (160ml) is added to the reaction mass after the completion of the reaction at 0- 5°C and stirred well and the pH of the reaction mass is adjusted to 6-6.5 using glacial acetic acid. Water (lit) is added to the reaction mass and stirred at 10-150C for 2hrs. The crystals formed are Filtered followed by water wash and drying under high vacuum.
Yield: 87%

Claims

We Claim:
1. A method for preparation of thiazolidinedione derivatives by reducing intermediates of thiazolidinedione derivatives having double bonds at temperature ranging between 0 to 250C comprises: a. adding sodium hydroxide solution into suspension of the intermediates of thiazolidinedione derivatives having double bonds in a mixture of polyethylene glycol and water; b. adding metal ligand complex catalysts of bivalent metals in presence of at least one complexing agent; c. adding sodium borohydride in alkaline solution and stirring; d. adding acetone to quench the reaction; e. adjusting pH with acid; f. isolating crystals by addition of water; and g. optionally re-using mother liquor as a solvent for future reduction reactions by basifying to pH values more than 9.
2. The method according to claim 1, wherein the bivalent metal is cobalt.
3. The method according to claim 1, wherein the alkaline solution is aqueous solution of sodium hydroxide.
4. The method according to claim 1, wherein the polyethylene glycol is polyethylene glycoI-400 grade.
5. The method according to claim 1, wherein the pH is adjusted in the range between 4 to 6.5.
6. The method according to claim 1, wherein the acid is selected from a group comprising citric acid, tartaric acid , acetic acid or mixtures thereof.
7. The method according to claim 1, wherein the thiazolidinedione derivatives are selected from a group comprising pioglitazone, englitazone, ciglitazone and rosiglitazone.
8. The method for preparation of thiazolidinedione derivatives as substantially herein described with accompanying examples.
PCT/IN2008/000230 2008-02-21 2008-04-08 A method for preparation of thiazolidinedione derivatives Ceased WO2009104200A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN00438/CHE/2008 2008-02-21
IN438CH2008 2008-02-21

Publications (2)

Publication Number Publication Date
WO2009104200A1 true WO2009104200A1 (en) 2009-08-27
WO2009104200A8 WO2009104200A8 (en) 2009-10-22

Family

ID=40985113

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2008/000230 Ceased WO2009104200A1 (en) 2008-02-21 2008-04-08 A method for preparation of thiazolidinedione derivatives

Country Status (1)

Country Link
WO (1) WO2009104200A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012153312A1 (en) 2011-05-11 2012-11-15 Ranbaxy Laboratories Limited Process for the purification of pioglitazone

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993013095A1 (en) * 1991-12-20 1993-07-08 The Upjohn Company A reduction method for substituted 5-methylene-thiazolidinediones
WO2004000810A1 (en) * 2002-06-19 2003-12-31 Eos Eczacibasi Ozgun Kimyasal Urunler Sanyi Ve Ticaret A.S. A process for the production of substituted phenyl ethers
WO2005021541A2 (en) * 2003-08-29 2005-03-10 Cipla Limited Process for the production of polymorphs of rosiglitazone maleate
WO2005058813A2 (en) * 2003-12-17 2005-06-30 Ranbaxy Laboratories Limited Thiodiazolidinedione, oxazolidinedione and diazolidinedione derivatives and their use as antidiabetic agents

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993013095A1 (en) * 1991-12-20 1993-07-08 The Upjohn Company A reduction method for substituted 5-methylene-thiazolidinediones
WO2004000810A1 (en) * 2002-06-19 2003-12-31 Eos Eczacibasi Ozgun Kimyasal Urunler Sanyi Ve Ticaret A.S. A process for the production of substituted phenyl ethers
WO2005021541A2 (en) * 2003-08-29 2005-03-10 Cipla Limited Process for the production of polymorphs of rosiglitazone maleate
WO2005058813A2 (en) * 2003-12-17 2005-06-30 Ranbaxy Laboratories Limited Thiodiazolidinedione, oxazolidinedione and diazolidinedione derivatives and their use as antidiabetic agents

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHANDRASEKHAR, S. ET AL., SYNLETT, vol. 3, 2004, pages 0522 - 0524 *
CLARK, D. A., J. MED. CHEM., vol. 34, 1991, pages 319 - 325 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012153312A1 (en) 2011-05-11 2012-11-15 Ranbaxy Laboratories Limited Process for the purification of pioglitazone

Also Published As

Publication number Publication date
WO2009104200A8 (en) 2009-10-22

Similar Documents

Publication Publication Date Title
Veisi et al. Chemoselective hydration of nitriles to amides using hydrated ionic liquid (IL) tetrabutylammonium hydroxide (TBAH) as a green catalyst
EP2300431B1 (en) Process for the manufacture of an intermediate in the synthesis of dabigatran
KR20090045920A (en) Chemical preparation of aromatic cyclopropane esters and amides
WO1993013095A1 (en) A reduction method for substituted 5-methylene-thiazolidinediones
RU2563459C2 (en) Method of producing phenyl-substituted heterocyclic derivative via coupling method using palladium compound
EP2404908A1 (en) Process for producing phenyl-substituted heterocyclic derivative through coupling using transition metal catalyst
WO2009104200A1 (en) A method for preparation of thiazolidinedione derivatives
CN105085510B (en) A kind of preparation method of the carboxylic acid tert-butyl ester of (S) 4 oxo 2 (carbonyl of thiazolidine 3) pyrrolidines 1
CN103910734B (en) A kind of DPP-4 inhibitor with piperazine structure
EP2888237B1 (en) Method for preparation of thiazole derivatives
WO2009148195A1 (en) 5-(4-hydroxybenzyl)thiazolidine-2,4-dione as intermediate for synthesis of thiazolidinedione based compounds and process for preparing the same
WO2008050661A1 (en) Method for producing asymmetric copper complex crystal
JP5009736B2 (en) Mannich reaction using cyclic amino ether
JP5854906B2 (en) Process for producing 4- [2- (5-ethyl-2-pyridyl) ethoxy] nitrobenzene or a salt thereof
CN106279144B (en) Method for preparing pioglitazone impurity C by one-pot method
CN101565362A (en) Method for synthesizing propionoin from propionaldehyde
US20060229453A1 (en) Process for the preparation of 5-[4-[2-[N-methyl-N-(2-pyridyl) amino] ethoxy] phenyl methyl] thiazolidine-2,4-dione maleate (rosiglitazone)
JP5441913B2 (en) Method for producing carbonyloxy compound
JP2008133261A (en) Method for producing asymmetric copper complex crystals
EP1786808B1 (en) Method for the preparation of rosiglitazone
JP5473303B2 (en) Process for producing methyl 2-bromo-3- {4- [2- (5-ethyl-2-pyridyl) ethoxy] phenyl} propionate
US20060135787A1 (en) Process for obtaining enantiomers of thienylazolylalcoxyethanamines
JP4769464B2 (en) Method for producing alcohol compound
CN120398757A (en) A preparation method of 2-propylpyridin-4(1H)-one acetate
CN104961722B (en) Method for preparing eprosartan intermediate by using reaction auxiliary agent

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08763722

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08763722

Country of ref document: EP

Kind code of ref document: A1