WO2008142706A2 - Novel process for the synthesis of pioglitazone and its salts thereof - Google Patents
Novel process for the synthesis of pioglitazone and its salts thereof Download PDFInfo
- Publication number
- WO2008142706A2 WO2008142706A2 PCT/IN2008/000315 IN2008000315W WO2008142706A2 WO 2008142706 A2 WO2008142706 A2 WO 2008142706A2 IN 2008000315 W IN2008000315 W IN 2008000315W WO 2008142706 A2 WO2008142706 A2 WO 2008142706A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- process according
- palladium
- pharmaceutically acceptable
- methanol
- Prior art date
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 relates to process for preparing Pioglitazone and it's pharmaceutically acceptable salts of Formula- VII known for the treatment of non-insulin dependent diabetes.
- Non-insulin-dependent diabetes mellitus is a metabolic disorder leading to long-term complications and premature atherosclerosis.
- Compounds of class like, sulfonylureas, biguanides were used for treatment of patients suffering from such disorders.
- Substituted arylthiazoiidinediones demonstrated potent activity towards non-insulin dependent diabetes.
- a number of thiazolidinedione derivatives which are disclosed as having hypoglycemic and hypolipidaemic activity.
- Pioglitazone selectively stimulates nuclear gamma-receptors, activated by peroxisome proliferator (PPAR). It modulates the transcription of the insulin sensitive genes involved in the control of glucose and lipid metabolism in the lipidic, muscular tissues and in the liver. Pioglitazone does not directly stimulate insulin secretion, but rather affects the insulin-synthetic function of the pancreas. Pioglitazone also reduces insulin resistance in the liver and peripheral tissues, increases the expense of insulin-dependent glucose, decreases withdrawal of glucose from the liver; reduces quantity of glucose, insulin and glycated haemoglobin in the bloodstream. Pioglitazone decreases the level of triglycerides and increases that of high-density lipoproteins without changing low-density lipoproteins and general cholesterol in patients with disorders of the lipid metabolism.
- PPAR peroxisome proliferator
- US Patent 4,812,570 discloses the process for the preparation of thiazolidinediones wherein, the time taken for the preparation of 4-[2-(5-ethyl-2-pyridyl)ethoxy]benzaldehyde is 10- 20 hours and the yields are low.
- This compound reacts with 2,4-thiazolidinedione in presence of piperidine in ethanol to give 5- ⁇ 4-[2-(5-ethyl-2-pyridyl)ethoxy]benzylidene ⁇ -2,4- thiazolidinedione which on further reduction yields pioglitazone.
- US Patent 5,554,758 and US Patent 6,100,403 disclose the process wherein the benzaldehyde ether derivatives are formed via Williamson coupling of 4-hydroxy benzaldehyde with a mesylate or tosylate of alcohol in presence of base. 4-[2-(5-ethyl-2-pyridyl)ethoxy] benzaldehyde formed, which is reacted with 2,4-thiazolidinedione to afford benzylidene-2,4- thiazolidinone. It is further subjected to reduction of the double bond of this compound result in the formation of crude compound of pioglitazone.
- US Patent 5,585,495 discloses the cobalt-catalysed reduction of the double bond of 5- ⁇ 4-[2-(5- ethyl-2-pyridyl)ethoxy]benzylidene ⁇ -2,4-thiazolidinedione.
- the method described is faster, easier and results in improved yields and convenient for scale up.
- Main aspect of the present invention is relates to provide an improved process for the production of Pioglitazone and its pharmaceutically acceptable salts.
- Another aspect of the present invention is relates to provide hydrogenation reaction is carried out with less quantity of catalyst and under less hydrogen pressure. Yet another aspect of the present invention is relates to provide improved quality of intermediate and final product.
- the present invention describes an improved process for the production of Pioglitazone and its pharmaceutically acceptable salts which comprises the steps of:
- Formula-I is reacted with RiSO 2 X (Formula-II) where R 1 is an alkyl or an aryl group and X is an halo group comprising the compounds methyl sulfonylchloride, ethyl sulfonylbromide, propyl sulfonylchloride, phenylsulfonyl chloride, /?-tolylsulfonyl chloride preferably alkyl sulfonylhalide to form compound of Formula-Ill in a solvent at the reaction temperature in the range of about -20°C to 60 0 C preferably -10 0 C to 40 0 C in presence of a base.
- Halogens are selected from fluorine, chlorine, bromine and iodine and alkyl groups are selected from Ci-C 4 -alkyls and aryl groups are selected from phenyl, tolyl etc.
- Suitable Solvent described above is selected from chlorinated solvents such as dichloromethane, dichloroethane, carbon tetrachloride, chloroform or hydrocarbon solvents such as benzene, toluene, xylene and others such as dimethylformamide.
- Bases are selected from inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, or organic bases selected form triethylamine, morpholine, N-methyl piperidine etc.
- Phase transfer catalysts is selected from benzyl tributylammonium bromide, benzyl triethylammonium chloride, tetrabutylammonium bromide, cetyl trimethylammonium chloride and like.
- Compound of Formula-IV obtained is condensed with 2,4-thiazolidinedione in a suitable solvent and a base.
- Suitable solvent is selected from alcohol such as methanol, ethanol, propanol; dimethyl formamide, dimethyl sulfoxide, acetonitrile, dioxane, acetic acid etc.
- the base is selected from amine such as ammonia, optionally substituted by C 1 -C 4 alkyl, pyrrolidine, piperidine, morpholine, piperazine, triethylamine, alkali metal/alkaline earth metal alkoxides, carbonates, bicarbonates, hydroxides like sodium methoxide, potassium carbonate, sodium bicarbonate, calcium hydroxide etc.
- Condensation reaction is generally conducted at 45 °C to reflux temperature and generally for about 1-45 hrs preferably 8 to 25 hrs.
- Condensed benzylidene derivative is converted to inorganic acid addition salt by the addition of mineral acid preferably sulphuric acid or phosphoric acid in Cj-C 4 alkanolic solvents, acetic acid and like to obtain the compound of Formula- V.
- Compound of Formula- V is catalytically reduced to obtain Formula- VI in presence of suitable solvent.
- suitable solvent is selected from alcohols such as methanol, ethanol, propanol, ethers such as dimethoxy ethane, dioxane, tetrahydrofuran etc., dimethyl formamide, ethylacetate, acetic acid etc., or mixtures thereof.
- Catalyst employed can be selected from palladium black, palladium on carbon, raney nickel or palladium on barium carbonate preferably palladium carbon.
- the reaction is carried out under a pressure of not more than 30 kg/cm 2 for 20-60 hours.
- the salt is neutralized with a base to form thizolidinedione.
- Base for neutralization is selected from amines such as ammonia, optionally substituted by Cj-C 4 alkyl, alkali metal/alkaline earth metal alkoxides, carbonates, bicarbonates, hydroxides like sodium methoxide, potassium carbonate, sodium bicarbonate, calcium hydroxide etc.
- amines such as ammonia, optionally substituted by Cj-C 4 alkyl, alkali metal/alkaline earth metal alkoxides, carbonates, bicarbonates, hydroxides like sodium methoxide, potassium carbonate, sodium bicarbonate, calcium hydroxide etc.
- Formula- VI thus obtained is converted to pharmaceutically acceptable salts by reacting with inorganic acids to form thiazolidinedione inorganic acid addition salts.
- Preferred mineral acid is hydrochloric acid.
- Hydrochloric acid is added as an alkanolic solution such as in methanol, ethanol, isopropanol, preferably as solution in methanol.
- Example-1 Preparation of 4- [2-(5-ethyl-2-py ridyl)ethoxy] benzaldehyde.
- Example-2 Preparation » of 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benziIidene-2,4- thiazolidinedione Sulfate.
- Example-4 Preparation of 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyI-2,4-thiazolidinedione Hydrochloride.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Present invention relates to an improved process for the preparation of thiazolidinedione derivatives. Further the invention provides the hydrogenation of acid addition salt of benzylidene compound with less reducing agent under low Hydrogen gas pressure to get substantially pure thiazolidinedione derivatives with improved yields.
Description
Title: Novel Process for the synthesis of Pioglitazone and its salts thereof
Field of invention:
The present invention relates to process for preparing Pioglitazone and it's pharmaceutically acceptable salts of Formula- VII known for the treatment of non-insulin dependent diabetes.
Background of the invention:
Non-insulin-dependent diabetes mellitus (NIDDM) is a metabolic disorder leading to long-term complications and premature atherosclerosis. Compounds of class like, sulfonylureas, biguanides were used for treatment of patients suffering from such disorders. Substituted arylthiazoiidinediones demonstrated potent activity towards non-insulin dependent diabetes. A number of thiazolidinedione derivatives which are disclosed as having hypoglycemic and hypolipidaemic activity.
Pioglitazone selectively stimulates nuclear gamma-receptors, activated by peroxisome proliferator (PPAR). It modulates the transcription of the insulin sensitive genes involved in the control of glucose and lipid metabolism in the lipidic, muscular tissues and in the liver. Pioglitazone does not directly stimulate insulin secretion, but rather affects the insulin-synthetic function of the pancreas. Pioglitazone also reduces insulin resistance in the liver and peripheral tissues, increases the expense of insulin-dependent glucose, decreases withdrawal of glucose from the liver; reduces quantity of glucose, insulin and glycated haemoglobin in the bloodstream. Pioglitazone decreases the level of triglycerides and increases that of high-density lipoproteins without changing low-density lipoproteins and general cholesterol in patients with disorders of the lipid metabolism.
US Patent 4,812,570, discloses the process for the preparation of thiazolidinediones wherein, the time taken for the preparation of 4-[2-(5-ethyl-2-pyridyl)ethoxy]benzaldehyde is 10- 20 hours and the yields are low. This compound reacts with 2,4-thiazolidinedione in presence of piperidine in ethanol to give 5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzylidene}-2,4- thiazolidinedione which on further reduction yields pioglitazone.
US Patent 5,554,758 and US Patent 6,100,403 disclose the process wherein the benzaldehyde ether derivatives are formed via Williamson coupling of 4-hydroxy benzaldehyde with a mesylate or tosylate of alcohol in presence of base. 4-[2-(5-ethyl-2-pyridyl)ethoxy] benzaldehyde formed, which is reacted with 2,4-thiazolidinedione to afford benzylidene-2,4- thiazolidinone. It is further subjected to reduction of the double bond of this compound result in the formation of crude compound of pioglitazone.
For the reduction of double bond several transition metal catalysed hydrogenation conditions are reported. They are low yielding and the reaction may not go for completion with starting material remaining as an impurity. To obtain reasonably pure samples in most of the reported conditions the reduction has been performed with 100-300 % w/w excess of Pd/C under very high pressures ranging between 50-100 kg cm"2 and the temperature varying between room temperature to 100°C.
US Patent 5,585,495 discloses the cobalt-catalysed reduction of the double bond of 5-{4-[2-(5- ethyl-2-pyridyl)ethoxy]benzylidene} -2,4-thiazolidinedione. The method described is faster, easier and results in improved yields and convenient for scale up. The method claims to eliminate the operational and safety problems associated with handling of pyrophoric Pd/C and high pressure hydrogenation.
Thus there is need for the alternate, more convenient, improved process for producing Pioglitazone and its pharmaceuticals acceptable salts on industrial scale.
Summary of the invention: Main aspect of the present invention is relates to provide an improved process for the production of Pioglitazone and its pharmaceutically acceptable salts.
Another aspect of the present invention is relates to provide hydrogenation reaction is carried out with less quantity of catalyst and under less hydrogen pressure.
Yet another aspect of the present invention is relates to provide improved quality of intermediate and final product.
Detailed description of the invention:
The present invention describes an improved process for the production of Pioglitazone and its pharmaceutically acceptable salts which comprises the steps of:
(a) reacting Formula (I) with Formula (II) to obtain Formula (III);
(b) coupling Formula (III) with/?-hydroxy benzaldehyde to get Formula (IV); (c) condensing of Formula (IV) with 2,4-thiazolidinedione in presence of base and suitable solvent to get Formula (V) and converting it to salt;
(d) reducing Formula (V) salt in the presence of catalyst under hydrogen pressure and solvent to get Formula (VI); and
(e) converting Formula (VI) into its pharmaceutically acceptable addition salts.
Accordingly the process in the present invention is described in scheme I
According to the scheme I5 Formula-I is reacted with RiSO2X (Formula-II) where R1 is an alkyl or an aryl group and X is an halo group comprising the compounds methyl sulfonylchloride, ethyl sulfonylbromide, propyl sulfonylchloride, phenylsulfonyl chloride, /?-tolylsulfonyl chloride preferably alkyl sulfonylhalide to form compound of Formula-Ill in a solvent at the reaction temperature in the range of about -20°C to 600C preferably -100C to 400C in presence of a base. Halogens are selected from fluorine, chlorine, bromine and iodine and alkyl groups are selected from Ci-C4-alkyls and aryl groups are selected from phenyl, tolyl etc.
Scheme-I
Compound of Formula-Ill is reacted with /?-hydroxybenzaldehyde in presence of a base in a suitable solvent in presence of a phase transfer catalyst to form compound of Formula-IV. The reaction is carried out at a temperature range of about 60°C to 100°C with the slow addition of compound of Formula-Ill for about 1-8 hrs preferably 2-5 hrs. The advantage of the process is minimization of vinyl pyridine impurity. The product yields obtained by this process are high compared to the prior art processes.
Suitable Solvent described above is selected from chlorinated solvents such as dichloromethane, dichloroethane, carbon tetrachloride, chloroform or hydrocarbon solvents such as benzene, toluene, xylene and others such as dimethylformamide. Bases are selected from inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, or organic bases selected form triethylamine, morpholine, N-methyl piperidine etc., Phase transfer catalysts is selected from benzyl tributylammonium bromide, benzyl triethylammonium chloride, tetrabutylammonium bromide, cetyl trimethylammonium chloride and like.
Compound of Formula-IV obtained is condensed with 2,4-thiazolidinedione in a suitable solvent and a base. Suitable solvent is selected from alcohol such as methanol, ethanol, propanol; dimethyl formamide, dimethyl sulfoxide, acetonitrile, dioxane, acetic acid etc., and the base is selected from amine such as ammonia, optionally substituted by C1-C4 alkyl, pyrrolidine, piperidine, morpholine, piperazine, triethylamine, alkali metal/alkaline earth metal alkoxides, carbonates, bicarbonates, hydroxides like sodium methoxide, potassium carbonate, sodium bicarbonate, calcium hydroxide etc., Condensation reaction is generally conducted at 45 °C to reflux temperature and generally for about 1-45 hrs preferably 8 to 25 hrs. Condensed benzylidene derivative is converted to inorganic acid addition salt by the addition of mineral acid preferably sulphuric acid or phosphoric acid in Cj-C4 alkanolic solvents, acetic acid and like to obtain the compound of Formula- V.
Compound of Formula- V is catalytically reduced to obtain Formula- VI in presence of suitable solvent. Suitable solvent is selected from alcohols such as methanol, ethanol, propanol, ethers such as dimethoxy ethane, dioxane, tetrahydrofuran etc., dimethyl formamide, ethylacetate, acetic acid etc., or mixtures thereof. Catalyst employed can be selected from palladium black, palladium on carbon, raney nickel or palladium on barium carbonate preferably palladium carbon. The reaction is carried out under a pressure of not more than 30 kg/cm2 for 20-60 hours. Finally the salt is neutralized with a base to form thizolidinedione. Base for neutralization is selected from amines such as ammonia, optionally substituted by Cj-C4 alkyl, alkali metal/alkaline earth metal alkoxides, carbonates, bicarbonates, hydroxides like sodium methoxide, potassium carbonate, sodium bicarbonate, calcium hydroxide etc. The advantage of the process is substantial conversion of starting material and formation of less impurity and also not involving high pressures. Purification steps are reduced which is industrially time consuming and laborious.
Formula- VI thus obtained is converted to pharmaceutically acceptable salts by reacting with inorganic acids to form thiazolidinedione inorganic acid addition salts. Preferred mineral acid is hydrochloric acid. Hydrochloric acid is added as an alkanolic solution such as in methanol, ethanol, isopropanol, preferably as solution in methanol.
The following non-limiting examples illustrate specific embodiments of the present invention. They are, not intended to be limiting the scope of present invention in any way.
Examples Example-1 : Preparation of 4- [2-(5-ethyl-2-py ridyl)ethoxy] benzaldehyde.
To a mixture of (5-ethyl-2-pyridyl)ethanol (1Og) and toluene (8ml) was added triethyl amine (8.5g). The mixture was cooled to -5 to -100C and slowly added Mesyl chloride solution (1Og in 20 ml toluene) and maintained the temperature of the reaction mass. DM water (50ml) was added to the reaction mass. Separated the organic layer and washed with DM water (50ml). Again separated the organic layer and extracted the aqueous layer with toluene (20ml). Sodium hydroxide solution (4.5g in 34 ml DM water), p-hydroxybenzaldehyde (12g) and tributyl benzylammonium chloride (3.5g) were slowly added to the organic layer at heating. The reaction mass was cooled and added water (120ml), separated the organic layer and extracted with IN sodium hydroxide (3 X 60ml). Filtered the reaction mass through hyflo bed and washed with toluene (10ml). Filtrate is dried with sodium sulfate (5g), distilled off toluene under vacuum. Yield: 12.5-15.O g.
Example-2: Preparation » of 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benziIidene-2,4- thiazolidinedione Sulfate. To a mixture of 4-[2-(5-ethyl-2-pyridyl)ethoxy]benzaldehyde (15g) and methanol (120ml) was added 2,4-thiazolidinedione (6g), piperidine (3g). The mixture was heated to reflux and added piperidine (0.5g). Cooled the reaction mass and adjusted the pH to 6.0-7.0 by 50% acetic acid solution. Filtered the solid and washed the cake with methanol (10ml). Added methanol (9ml) to the wet material and heated to reflux. Cooled the reaction mass, filtered and washed the cake with methanol (10ml). Added methanol (170ml) to the wet material and cooled the reaction mass. Adjusted the pH of the reaction mass to 1.0-2.0 with 25% sulfuric acid. Filtered the reaction mass and washed the cake with methanol (1 OmI). Dry the solid. Yield: 12-16g.
Example-3: Preparation of 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl-2,4-thiazolidinedione.
5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzilidene-2,4-thiazolidinedione Sulfate (1Og)3 acetic acid (60ml) and DM water (35ml) was heated to 50-700C. Added 10% Pd/C (5g) and applied hydrogen gas pressure (9-12kg/cm2) and maintained. Added 10% Pd/C with acetic acid. Cooled the reaction mass, filtered and washed with acetic acid (10 ml). Distilled off the filtrate and methanol (100ml) was added. Adjusted pH of the reaction mass to 6.5-7.0 with aqueous ammonia solution, filtered and washed with methanol (10ml). Added DM water (50ml) to the wet material, filter and wash the cake with DM water (20ml). Dry the material under vacuum till LOD is <2.0%w/w to get 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl-2,4-thiazolidinedione. Yield: 5.5-6.5g.
Example-4: Preparation of 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyI-2,4-thiazolidinedione Hydrochloride.
5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl-2,4-thiazolidinedione (1Og) and methanolic HCl (60ml) was heated to 40-600C. Filtered the reaction mass and washed the cake with methanolic HCl (10ml). Heated the reaction mass to 40-600C and slowly cooled. Added seeding material (50mg) and maintained the reaction mass for 1-2 hrs. Filtered the reaction mass and washed with chilled ethanol (10ml). Added ethanol (100ml) to the wet material and heated the reaction mass to reflux. Cooled the reaction mass to room temperature, filtered and washed the cake with ethanol (10ml). Dry the material under vacuum till LOD is <5.0%w/w to get 5-[4-[2-(5-ethyl-2- pyridyl)ethoxy]benzyl-2,4-thiazolidinedione HCl. Yield: 5.5-7.5g.
Claims
1. A process for the production of Pioglitazone and its pharmaceutically acceptable salts which comprises the steps of: (a) reacting Formula (I) with Formula (II) to obtain Formula (III);
(b) coupling Formula (III) with p-hydroxy benzaldehyde to get Formula (IV);
(c) condensing of Formula (IV) with 2,4-thiazolidinedione in presence of base and suitable solvent to get Formula (V) and converting it to salt;
(d) reducing Formula (V) salt in the presence of catalyst under hydrogen pressure and solvent to get Formula (VI); and
(e) converting Formula (VI) into its pharmaceutically acceptable addition salts.
2. The process according to claim 1, wherein Formula II is methyl sulfonylchloride, ethyl sulfonylbromide, propyl sulfonylchloride, phenylsulfonyl chloride and />-tolylsulfonyl chloride.
3. The process according to claim 1, wherein base used is amine such as ammonia, optionally substituted C1-C4 alkyl, pyrrolidine, piperidine, morpholine, piperazine, triethylamine, alkali/alkaline earth metal alkoxide, carbonate, bicarbonate, hydroxide such as sodium methoxide, potassium carbonate, sodium bicarbonate, calcium hydroxide.
4. The process according to claim Ic, wherein suitable solvent used is alcohol such as methanol, ethanol, propanol; dimethyl formamide; dimethyl sulfoxide; acetonitrile; dioxane and acetic acid.
5. The process according to claim 1, wherein catalyst used is palladium black, palladium on carbon, raney nickel or palladium on barium carbonate.
6. The process according to claim Id, wherein solvent used is alcohol such as methanol, ethanol, propanol; ether such as dimethoxy ethane, dioxane, tetrahydrofuran; dimethyl formamide; ethylacetate and acetic acid or mixture thereof.
7. The process according to claim 1, wherein hydrogen pressure is not more than 30 kg/cm2.
8. A process for the production of Pioglitazone and its pharmaceutically acceptable salts which comprises the steps of: a) reducing Formula (V) sulfate salt in the presence of catalyst under hydrogen pressure to get Formula (VI); and b) converting Formula (VI) into its pharmaceutically acceptable addition salts.
9. The process according to claim 8, wherein catalyst used is palladium black, palladium on carbon, raney nickel or palladium on barium carbonate.
10. The process according to claim 8 wherein solvent used for reduction reaction is alcohol such as methanol, ethanol, propanol; ether such as dimethoxy ethane, dioxane, tetraliydrofuran; dimethyl formamide; ethylacetate and acetic acid or mixture thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1050CH2007 | 2007-05-18 | ||
| IN1050/CHE/2008 | 2007-05-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2008142706A2 true WO2008142706A2 (en) | 2008-11-27 |
| WO2008142706A3 WO2008142706A3 (en) | 2009-12-03 |
Family
ID=40032272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2008/000315 WO2008142706A2 (en) | 2007-05-18 | 2008-05-19 | Novel process for the synthesis of pioglitazone and its salts thereof |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2008142706A2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101824032A (en) * | 2010-04-23 | 2010-09-08 | 浙江华海药业股份有限公司 | Improved technological method for preparing pioglitazone hydrochloride |
| WO2012153312A1 (en) | 2011-05-11 | 2012-11-15 | Ranbaxy Laboratories Limited | Process for the purification of pioglitazone |
| WO2015027067A3 (en) * | 2013-08-23 | 2015-05-07 | Virginia Commonwealth University | Ester nitrates derivatives of aromatic aldehydes with multiple pharmalogic properties to treat sickle cell disease |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0257781A1 (en) * | 1986-07-24 | 1988-03-02 | Takeda Chemical Industries, Ltd. | A method for producing thiazolidinedione derivatives |
| US20060252803A1 (en) * | 2001-12-20 | 2006-11-09 | Ben-Zion Dolitzky | Hydrogenation of precursors to thiazolidinedione antihyperglycemics |
-
2008
- 2008-05-19 WO PCT/IN2008/000315 patent/WO2008142706A2/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0257781A1 (en) * | 1986-07-24 | 1988-03-02 | Takeda Chemical Industries, Ltd. | A method for producing thiazolidinedione derivatives |
| US20060252803A1 (en) * | 2001-12-20 | 2006-11-09 | Ben-Zion Dolitzky | Hydrogenation of precursors to thiazolidinedione antihyperglycemics |
Non-Patent Citations (1)
| Title |
|---|
| OKAMOTO, K. ET AL.: 'Recoverable, Reusable, Highly Active, and Sulfur-Tolerant Polymer Incarcerated Palladium for Hydrogenation' JOURNAL OF ORGANIC CHEMISTRY vol. 69, no. 8, 2004, pages 2871 - 2873 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101824032A (en) * | 2010-04-23 | 2010-09-08 | 浙江华海药业股份有限公司 | Improved technological method for preparing pioglitazone hydrochloride |
| WO2012153312A1 (en) | 2011-05-11 | 2012-11-15 | Ranbaxy Laboratories Limited | Process for the purification of pioglitazone |
| WO2015027067A3 (en) * | 2013-08-23 | 2015-05-07 | Virginia Commonwealth University | Ester nitrates derivatives of aromatic aldehydes with multiple pharmalogic properties to treat sickle cell disease |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008142706A3 (en) | 2009-12-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7863300B2 (en) | Process to prepare pioglitazone via several novel intermediates | |
| WO1996038428A1 (en) | N-benzyldioxothiazolidylbenzamide derivatives and process for producing the same | |
| BRPI0413991B1 (en) | ppar activating compound and pharmaceutical composition containing the same | |
| JPS6242903B2 (en) | ||
| EP1387843B1 (en) | Method for obtaining pioglitazone as an antidiabetic agent | |
| JP2000515133A (en) | Hypoglycemic and hypolipidemic compounds | |
| EP0927173B1 (en) | substituted [2-(1-piperazinyl)ethoxy]methyl | |
| JPH0784446B2 (en) | Novel substituted thiazole and oxazole compounds | |
| WO2008142706A2 (en) | Novel process for the synthesis of pioglitazone and its salts thereof | |
| WO2005026095A1 (en) | Process for the preparation of roflumilast | |
| US4824833A (en) | Benzoxazine derivatives | |
| MX2008001246A (en) | A process for the preparation of substituted phenyl ether compounds and rosiglitazone. | |
| JP2007512240A (en) | Method for producing thiazolidinedione | |
| US20060178519A1 (en) | Process for preparing tegaserod | |
| US8993773B2 (en) | Process to prepare pioglitazone via several novel intermediates | |
| WO1984001945A1 (en) | Phenoxyaminopropanol derivatives | |
| US20090216024A1 (en) | Processes for making pioglitazone and compounds of the processes | |
| KR100697982B1 (en) | Manufacturing method of rosiglitazone | |
| JPH1087641A (en) | N-benzyldioxothiazolidylbenzamide derivative and its production | |
| KR100697983B1 (en) | Novel intermediate, manufacturing method of pioglitazone using it | |
| CN115215856A (en) | Preparation method of PPAR delta agonist finadepa and intermediate thereof | |
| KR100791399B1 (en) | Process for preparing of pioglitazone hcl | |
| CA2251637C (en) | Novel substituted [2-(1-piperazinyl)ethoxy]methyl | |
| FR2614619A1 (en) | Process for the preparation of N-(2-chlorobenzyl)-2-(2-thienyl)ethylamine | |
| KR100791400B1 (en) | Process for preparing of thiazolidinedione derivatives |
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: 08776668 Country of ref document: EP Kind code of ref document: A2 |
|
| NENP | Non-entry into the national phase in: |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 08776668 Country of ref document: EP Kind code of ref document: A2 |