WO2009027990A1 - Salts of montelukast and process therefor - Google Patents
Salts of montelukast and process therefor Download PDFInfo
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- WO2009027990A1 WO2009027990A1 PCT/IN2007/000492 IN2007000492W WO2009027990A1 WO 2009027990 A1 WO2009027990 A1 WO 2009027990A1 IN 2007000492 W IN2007000492 W IN 2007000492W WO 2009027990 A1 WO2009027990 A1 WO 2009027990A1
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- UCHDWCPVSPXUMX-XNTDXEJSSA-N CC(C)(c1c(CCC(c2cccc(/C=C/c(cc3)nc4c3ccc(Cl)c4)c2)SCC2(CC(O)=O)CC2)cccc1)O Chemical compound CC(C)(c1c(CCC(c2cccc(/C=C/c(cc3)nc4c3ccc(Cl)c4)c2)SCC2(CC(O)=O)CC2)cccc1)O UCHDWCPVSPXUMX-XNTDXEJSSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
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Abstract
The present invention relates to new salts (II) of Montelukast (I) and process for preparing these salts where B is ammonia, benzylamine or phenyl hydrazine. The invention also provides a process for preparation amine salts comprising (a) dissolving/ suspending the Montelukast free acid of formula (I) in an organic solvent (b) reacting with an amine (c) isolating the amine salt of formula (II) by adding optionally another anti-solvent, and (d) optionally drying the isolated solid under vacuum. The invention provides a process for preparation of sodium salt of montelukast acid comprising lowering pH of aqueous solution of amine salt of montelukast having formula II to 5.0±0.5, raising pH to above 8.0 using source of sodium ion, and isolating, the sodium salt by crystallization.
Description
SALTS OF MONTELUKAST AND PROCESS THEREFOR.
The invention particularly relates to amine salts of montelukast having formula II
II where B represents ammonia, benzyl amine, or phenyl hydrazine.
The invention also provides a process for preparing these amine salts and sodium salt with increased purity, and solubility and reduced toxicity. The process further is cost effective, environment friendly, and easily scale up to commercial level. The invention also provides a process for conversion of these amine salts to montelukast acid with high purity at a reduced cost and its further conversion to sodium salt
BACKGROUND OF THE INVENTION
The biosynthesis of leukotrienes, which are produced in living system from arachidonic acid, begins with the action of enzyme 5-lipoxygenase on arachidonic acid and epoxide known as Leukotriene A4 (LT A4) is produced. These leukotriene A4 are converted into other leukotrienes by enzymatic process. The compound of formula (I) is leukotriene antagonists and useful agent in the treatment of asthma, inflammation and allergic diseases.
European patent No. 480,717 describes certain quinoline compounds, including Montelukast. The reported synthesis of compound of formula (I) as described in U.S. Pat. No. 5,565,473 proceeds through corresponding methyl ester which is formed by coupling of methyl- l-(mercaptomethyl) cyclopropane acetate with mesylate of formula (III) generated in situ.
(III)
The free acid (I) is obtained by hydrolysis of its methyl ester and is converted directly to its sodium salt.
This process requires tedious chromatographic purification of methyl ester intermediate and/ or the final product. Furthermore, the yield of product is quite low. Therefore, this process is not suitable for large scale production.
Furthermore, U.S. pat. No. 5,614,632 discloses the preparation of DCHA salt of Montelukast having formula (IV) for its purification which is ultimately converted into its sodium salt after neutralization of DCHA.
Acetic (IV) acid
Where A is Dicyclohexylamine (DCHA).
U.S. pat. No. 0107612 discloses the preparation of tertiary butylamine and phenylethylamine salt of the compound of formula (I).
Although certain processes of its preparation and purification are known, still an improved and efficient process is required for preparation and purification of compound of formula (I) which can be utilized in the scale-up of the product having appropriate yield and quality.
SUMMARY OF THE INVENTION
The first aspect of this invention is to get new amine salts (organic amines and inorganic amines based) of Montelukast.
According to another aspect of the invention there is provided a process for the preparation of salts of Montelukast of formula (II), which comprises, a) preparing solution/ suspension of the Montelukast free acid of formula I in an organic solvent like C1-C5 ester solvents e.g. ethyl acetate, isopropyl acetate etc; aromatic hydrocarbons like toluene, benzene, xylene etc; ether solvents like tetrahydrofuran, diethyl ether, diisopropyl ether etc; halogenated hydrocarbons like dichloromethane, chloroform etc; ketone solvents like acetone, methyl isobutyl ketone etc. or a mixture thereof b) reacting with amines preferably ammonia, benzylamine or phenyl hydrazine c) isolating the amine salt of formula (II) by adding optionally another antisolvent e.g. hexane, heptane, toluene or a mixture thereof d) optionally drying amine salt of formula (II) at 40-45°C under vacuum.
In accordance with the other aspect of this invention there is provided a process for preparing Montelukast acid and/or montelukast sodium salt from amine salt comprising lowering pH of aqueous solution of amine salt to pH 5.0 ± 0.5 in order . to get montelukast acid, raising pH above 8.0 using source of sodium ion, purifying if so desired, reconverting to acid by acidification and crystallizing acid so obtained by conventional methods
hi accordance with another aspect of the invention there is provided a process for the preparation of amine salt of Montelukast of formula (II) and hence of Montelukast free acid of formula (I) in pure form, by hydrolysis of Montelukast methyl ester (V).
Thus, according to this invention, there are provided new salts of Montelukast of formula (II) having distinct XRD profile and process along with use of these amine
salts. It resulted in the increased purity of the salts of Montelukast of formula (II). These salts were converted into Montelukast free acid of formula (I) of high purity by treatment with acids in toluene-water or water.
BRIEF DESCRIPTION OF THE FIGURES:
FIG.l depicts the X-ray powder diffraction pattern of ammonium salt of Montelukast of formula II.
FIG.2 depicts the X-ray powder diffraction pattern of Benzylamine salt of Montelukast of formula II.
FIG.3 depicts the X-ray powder diffraction pattern of Phenyl hydrazine salt of Montelukast of formula II.
DETAILED DESCRIPTION OF THE INVENTION
The first aspect of this invention is to get new salts (organic amines and inorganic amines base) of Montelukast having X-ray powder diffraction pattern as shown in figures 1 to 3 accompanying this specification.
According to another aspect, this invention provides a process for the preparation of ammonium, benzylamine and phenyl hydrazine salt of Montelukast of formula (II) which comprises, a) dissolving/ suspending the Montelukast free acid of formula I in an organic solvent b) reacting with amines c) isolating the amine salt of formula (II)
The organic solvents used for dissolution or suspension include (1) C1-C4 ester solvents selected from ethyl acetate, isopropyl acetate; (2) aromatic hydrocarbons selected from toluene, benzene, xylene; (3) ether solvents selected from tetrahydrofuran, diethyl ether, diisopropyl ether; (4) halogenated hydrocarbons selected from dichloromethane, chloroform; (5) ketone solvents selected from acetone, methyl isobutyl ketone etc. or a mixture of two or more solvents The amines employed are selected from ammonia, benzylamine or phenyl hydrazine.
Amine salts are isolated by seeding or cooling or by adding another anti solvent selected hexane, heptane, toluene or a mixture thereof or by crystallization. The salts so obtained are dried at 40-45°C under vacuum.
The salts (II), thus obtained, have the advantage that they resulted in the increased purity of the product e.g. the amine salt of formula (II) having purity >99% are obtained using ammonia, benzylamine or phenyl hydrazine starting from Montelukast free acid of formula (I) having HPLC purity even <80%. Out of three salts of formula (II), although all salts afford high purity of compound of formula (II), ammonium salt gives best results as far as yield and quality of compound of formula (II) is concerned. The ammonium salt of formula (II) has also following advantages over known DCHA, t-butylamine and phenylethylamine salts of Montelukast:
1. Use of ammonia to get ammonium salt is comparatively safer over use of DCHA to prepare DCHA salt, due to less toxicity. LD50 of DCHA is 373 mg/kg whereas LC50 of ammonia is 2000 ppm/ 4H. Thus Ammonia is less toxic than DCHA.
2. Ammonia is highly water soluble and there is no possibility of its carryover, to final product when ammonium salt is cleaved with acid to get Montelukast free acid in water or water-organic solvent mixture. Whereas possibility of DCHA carryover is more when DCHA salt is cleaved using above process to get Montelukast free acid due to DCHA being sparingly soluble in water.
3. On burning of DCHA there is formation of highly toxic gases like carbon mono oxide and carbon dioxide whereas no such gases are produced on burning ammonia.
4. DCHA is cancer suspect chemical whereas ammoia has no such evidence.
5. The ammonium salt of formula (II) of Montelukst can easily be used as API.
Thus, it is apparent that though t-butylamine and phenylethylamine salts of Montelukast are advantageous over DCHA, ammonium salt is far superior to t- butylamine and phenylethylamine salts with regard to yield. Furthermore, ammonium salt is more environmental friendly, less toxic and cost effective in comparison to other salts.
The readily isolable amine salts of formula (II) resulted in the effective purification of a compound of formula (I) in presenc; of acids in water or toluene- water mixture.
The ammonium salt of formula (II) has a unique advantage over DCHA, benzyl or 5 phenyl hydrazine salts that it affords Montelukast free acid of formula (I) simply by heating or by acidification in water in comparatively higher yield than other amine salts (in water or toluene-water) whereas other salts including DCHA salt are not completely converted to Montelukast free acid of formula (I) in water and requires a mixture of toluene or other water immiscible organic solvents and water. 0
Accordingly, another aspect of the present invention provides a process for the preparation of sodium salt of Montelukast acid of formula (I) from its amine salt of formula (II) which comprises, 5 a) reacting the suspension of amine salt of formula (II) in water or water immiscible organic solvents like toluene, methyl isobutylketone, ethyl acetate etc. and water mixture with acids b) isolating the solid obtained in water or separating water immiscible solvent layer from water and crystallizing the product just by raising pH to above 8.0 using souece of0 sodium ion . c) drying the sodium salt of Montelukast acid of formula (I).
The other aspect of the present invention provides a process for the preparation of Montelukast acid of formula (I) from its ammonium salt of formula (II) which5 comprises, a) stirring a suspension of Montelukast acid ammonium salt (II) in an organic solvent like toluene, ethyl acetate etc or water, converting to sodium salt in a known manner, b) isolating the product by filteration. c) drying the sodium salt of Montelukast free acid of formula (I). θ'
The other aspect of the present invention provides a process for the preparation of Montelukast acid of formula (I) from its ammonium salt of formula (II) which comprises,
a) heating of Montelukast acid ammonium salt (II) directly or in a suitable organic solvent like C1-C4 ester solvents e.g. ethyl acetate, isopropyl acetate etc; aromatic hydrocarbons like toluene, benzene, xylene etc; ether solvents like tetrahydrofuran, diethyl ether, diisopropyl ether etc; halόgenated hydrocarbons like dichloromethane, chloroform etc; ketone solvents like acetone, methyl isobutyl ketone etc. or a mixture of two or more solvents b) drying the Montelukast free acid of formula (I) as such or after filtration.
EXAMPLE I
To a solution of lOOg of Montelukast acid (I) in ethyl acetate (600ml) with stirring at 20-250C, ammonia gas was purged for lhr. or ammonical ethyl acetate( 17-20%, 25ml) was added. Then hexane (600ml) was slowly added with continuous stirring. After complete addition of hexane, the slurry was further stirred for 10-15 hr. at 20-25°C. The solid, thus obtained was filtered and was given slurry washing with hexane (100ml) and material was suck dried. The product was dried at 40-45°C for 5-6 hr. (100gm; 97%)
EXAMPLE II
To a suspension of ammonium salt (II) of Montelukast (10Og) in water (500ml.) at 25- 300C, acetic acid (1Og) was added dropwise with continuous stirring. After complete addition of acetic add, the reaction mixture was stirred at 25-300C for 5-6 hr. The solid, thus obtained, was filtered and washed with water (100ml.) and material was suck dried. Then the product was dried at 40-450C for 5-6 hr. under vacuum. (87.3g; 90%)
EXAMPLE III
To a solution of lOOg of Montelukast (I) in ethyl acetate (600ml) with stirring at 20- 25°C, benzylamine (23.58g) was added drop wise with continuous stirring. The reaction mixture was stirred for 1 hr. Then Hexane (600ml) was slowly added with continuous stirring at 20-25 °C. After complete addition of hexane, the reaction mixture was further stirred for 10-15 hr. at 20-250C. The solid, thus obtained was filtered and
was given slurry washing with hexane (100ml) and material was suck dried. The product was dried at 40-45 °C for 5-6 hr.
(112g; 95%)
EXAMPLE IV
To a suspension of benzylamine salt (II) of Montelukast (10Og) in toluene (500ml.) and water (500ml.) at 25-30°C, acetic acid (1Og) was added drop wise with continuous stirring. After complete addition of acetic acid, the reaction mixture was stirred at 25- 300C for 5-6 hr. The toluene layer was separated and washed with water (100ml.). The toluene layer was stirred at 25-30°C for 7-8 hr. The solid, thus obtained was filtered and dried at 40-45°C for 5-6 hr under vacuum. (68g; 81%) EXAMPLE V
To a solution of lOOg of Montelukast (I) in ethyl acetate (600ml) with stirring at 20- 25°C, phenylhydrazine (23.80g) was added drop wise with continuous stirring. The reaction mixture was stirred for 1 hr. Then hexane (600ml) was slowly added with continuous stirring at 20-25°C. After complete addition of hexane, the reaction mixture was further stirred for 10-15 hr. at 20-25°C. The solid, thus obtained, was filtered and was given slurry washing with hexane (100ml) and material was suck dried. The product was dried at 40-450C for 5-6 hr. (60gm; 51%)
EXAMPLE VI
To a suspension of phenylhydrazine salt (II) of Montelukast (6Og) in toluene (300ml.) and water (300ml.) at 25-30°C, acetic acid (6g) was added drop wise with continuous stirring. After complete addition of acetic acid, the reaction mixture was stirred at 25- 300C for 5-6 hr. The toluene layer was separated and washed with water (100ml.). The toluene layer, thus obtained, was stirred at 25-300C for 7-8hrs. The solid was filtered and dried at 40-450C for 5-6 hr under vacuum. (43.1g; 85%)
EXAMPLE VII
To a suspension of lOOg of Montelukast methyl ester (V) in methanol (400ml) and THF (400ml), one molar aq. caustic solution (347ml) is added at 25-30°C and the reaction mixture is stirred at 25-30°C for 24hr.The progress of reaction is monitored by HPLC. After completion of reaction, methanol-THF is recovered at reduced pressure and a mixture of water (1000ml) and methanol (400ml) is added and pH of solution is adjusted to 8-9 using acetic acid. The reaction solution is washed with toluene (3χl00ml) and aq. layer is separated. The pH of aq. layer is adjusted to 5.0-5.5 using acetic acid and product is extracted in ethyl acetate (3 x 200ml) followed by washing of ethyl acetate layer with water (2 x 100ml). Organic layer is dried over anhydrous Na2SO4,
To the above ethyl acetate layer with stirring at 20-25°C, ammonia gas was purged for lhr. or ammonical ethyl acetate (17-20%, 25ml) was added. Then hexane (600ml) was slowly added with continuous stirring. After complete addition of hexane, the slurry was further stirred for 10-15 hr. at 20-25°C. The solid, thus obtained was filtered and was given slurry washing with hexane (100ml) and material was suck dried. The product was dried at 40-45°C for 5-6 hr. (9Og; 92.15%)
Example VIII
To a suspension of lOOg of Montelukast methyl ester (V) in methanol (400ml) and THF (400ml), one molar aq. caustic solution (347ml) is added at 25-30°C and the reaction mixture is stirred at 25-30°C for 24hr.The progress of reaction is monitored by HPLC. After completion of reaction, methanol-THF is recovered at reduced pressure and a mixture of water (1000ml) and methanol (400ml) is added and pH of solution is adjusted to 8-9 using acetic acid. The reaction solution is washed with toluene (3 x 100ml) and aq. layer is separated. The pH of aq. layer is adjusted to 5.0-5.5 using acetic acid and product is extracted in ethyl acetate (3χ200ml) followed by washing of ethyl acetate layer with water (2χ 100ml). Organic layer is dried over anhydrous Na2SO4,
To the above ethyl acetate layer at 20-25°C, benzylamine (23.58g) was added drop wise with continuous stirring. The reaction mixture was stirred for 1 hr. Then Hexane (600ml) was slowly added with continuous stirring at 20-25°C. After complete addition
of hexane, the reaction mixture was further stirred for 10-15 hr. at 20-25°C. The solid, thus obtained was filtered and was given slurry washing with hexane (100ml) and material was suck dried. The product was dried at 40-45 °C for 5-6 hr. (92.5g; 94%)
Example IX
To a suspension of lOOg of Montelukast methyl ester (V) in methanol (400ml) and THF (400ml), one molar aq. caustic solution (347ml) is added at 25-30°C and the reaction mixture is stirred at 25-3O0C for 24hr.The progress of reaction is monitored by HPLC. After completion of reaction, methanol-THF is recovered at reduced pressure and a mixture of water (1000ml) and methanol (400ml) is added and pH of solution is adjusted to 8-9 using acetic acid. The reaction solution is washed with toluene (3xl00ml) and aq. layer is separated. The pH of aq. layer is adjusted to 5.0-5.5 using acetic acid and product is extracted in ethyl acetate (3 x 200ml) followed by washing of ethyl acetate layer with water (2* 100ml). Organic layer is dried over anhydrous Na2SO4,
To the above ethyl acetate layer at 20-25°C, phenylhydrazine (23.8Og) was added drop wise with continuous stirring. The reaction mixture was stirred for 1 hr. Then hexane (600ml) was slowly added with continuous stirring at 20-25°C. After complete addition of hexane, the reaction mixture was further stirred for 10-15 hr. at 20-250C. The solid, thus obtained, was filtered and was given slurry washing with hexane (100ml) and material was suck dried. The product was dried at 40-450C for 5-6 hr. (58g, 50%)
Example Xi,
To a suspension of ammonium salt (II) of Montelukast in toluene is stirred at 50-600C for 6hrs and the Montelukast acid, thus obtained, is filtered and washed with toluene. The product is dried at 40-450C for 5-6 hr under vacuum.
ADVANTAGES
1. The main advantage of isolable amine salts of formula (II) of Montelukast is that they resulted in the increased purity of amine salt of formula (II) and hence of Montelukast free acid of formula (I).
2. The ammonium salt of formula (II) of Montelukast is readily convertible to Montelukast in wate*1 these use of solvent can be avoided. Furthermore, the process ■ >f ammonium salt of Montelukast of formula (II) is cost effective, echo-friendly and suitable for scale-up. 3. The ammonium salt of formula (II) of Montelukst can easily be used as API.
4. All the new amine salts described herein, specially ammonium salt resulted in the increased yield of Montelukast free acid of formula (I).
5. The amine salt of Montelukast acid (II) can be converted directly into Montelukast acid (I) by stirring at higher temperature.
Claims
WE CLAIM: 1. Novel salts of montelukast having formula II
2. A process for the preparation of salts of Montelukast acid formula (II) as claimed in claim 1 , which comprises a) dissolving/ suspending the Montelukast free acid of formula (I) in an organic solvent. b) reacting with an amine. c) isolating the amine salt so produced.
3. The process as claimed in claim 2, wherein the organic solvent used in step (a) include C1-C4 aliphatic esters; aromatic hydrocarbons; cyclic or acyclic ethers; halogenated hydrocarbons; aliphatic ketones or a mixture thereof
4. The process as claimed in claim 3, wherein the Cj-C4 aliphatic esters used is selected from ethyl acetate, isopropyl acetate.
5. The process as claimed in claim 3, wherein the aromatic hydrocarbons used is selected from toluene, benzene, xylene.
6. The process as claimed in claim 2, wherein the cyclic or acyclic ethers used is selected from tetrahydrofuran, diethyl ether, diisopropyl ether.
7. The process as claimed in claim 2, wherein the halogenated hydrocarbons used is selected from dichloromethane, chloroform; aliphatic ketones preferably selected from acetone, methyl isobutyl ketone or a mixture thereof.
8. The process as claimed in claim 2, wherein the amines used in step (b) are selected from benzylamine, phenylhydrazine and ammoma.
9. The process as claimed in claim 2, wherein the isolation is carried out by adding anti-solvent comprising aromatic hydrocarbons selected from toluene, benzene, xylene; C5-C8 aliphatic straight or branched chain hydrocarbons selected from hexane, heptane or a mixture thereof .
10. The process as claimed in claim 2, wherein the isolation is carried out by crystallization.
11. The process as claimed in claim 11, wherein the crystallization is carried out by seeding.
12. A process for the preparation of sodium salt of Montelukast acid of formula (I), which comprises:
(a) lowering pH of aqueous solution of amine salt of montelukast having formula II wherein 'B" has the meaning as defined herein above in claim 1, to 5.0±0.5,
(b) raising pH to above 8.0 using source of sodium ion, and (c) isolating the sodium salt by crystallization.
13. A process for the preparation of sodium salt of Montelukast acid of formula (I), which comprises a) reacting the suspension of amine salt of formula (II) in water or water immiscible organic solvents with acid. b) isolating the Montelukast free acid so obtained in water or separating water immiscible solvent layer from water converting to its sodium salt by conventional method and crystallizing the product.
14. A process as claimed in claim 15, wherein the organic solvents used in step (a) comprising aromatic hydrocarbons selected from toluene, benzene, xylene; aliphatic esters selected from ethyl acetate, isopropyl acetate; aliphatic ketones selected from acetone, methyl isobutyl ketone etc , water or a mixture thereof.
15. A process as claimed in claim 15, wherein the acid used in step (a) is selected from acetic acid, tartaric acid, sulfuric acid , hydrochloric acid or a mixture thereof.
16. A process as claimed in claim 15, wherein the organic solvents used in step (b) for crystallization are selected from aromatic hydrocarbons like toluene, benzene, xylene etc; aliphatic esters like ethyl acetate, isopropyl acetate etc ; halogenated hydrocarbons like dichloromethane, chloroform etc , water or a mixture thereof..
17. A process for the preparation of sodium salt of Montelukast acid of formula (I) , which comprises a) stirring a suspension of Montelukast acid ammonium salt (II) in an organic solvent. b) isolating the Montelukast acid (I) by filtration, c) drying the Montelukast free acid of formula (I).
18. A process as claimed in claim 17, wherein the organic solvent used in step (a) is selected from aromatic hydrocarbons like toluene, benzene, xylene etc; aliphatic esters like ethyl acetate, isopropyl acetate etc ; C5-C8 straight or branched chain aliphatic hydrocarbons like, hexane, heptane etc or water or a mixture thereof.
\&. A process as claimed in claim 17, wherein the stirring is carried out at a temperature ranging from 20-1000C , more preferably 30-800C; most preferably
50-700C. %9. A process ar, claimed in claim 17, wherein the isolation is conducted at a temperature ranging from 10-600C, more preferably 20-400C; most preferably 25-350C.
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IN1822/DEL/2007 | 2007-08-29 | ||
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011121091A1 (en) | 2010-03-31 | 2011-10-06 | Krka, D.D., Novo Mesto | Efficient synthesis for the preparation of montelukast and novel crystalline form of intermediates therein |
WO2012015255A3 (en) * | 2010-07-30 | 2012-04-26 | Dong Kook Pharm. Co., Ltd | Novel montelukast 4-halobenzylamine salt and method for preparing montelukast sodium salt by using the same |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995018107A1 (en) * | 1993-12-28 | 1995-07-06 | Merck & Co., Inc. | Process for the preparation of leukotriene antagonists |
US20050234241A1 (en) * | 2004-04-15 | 2005-10-20 | Venkataraman Sundaram | Process for the preparation of [R-(E)-1-[[[1-[3-[2-[7-chloro-2-quinolinyl]ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (montelukast) and its pharmaceutically acceptable salts |
WO2006008751A2 (en) * | 2004-07-19 | 2006-01-26 | Matrix Laboratories Ltd | Process for the preparation of montelukast and its salts |
WO2006043846A1 (en) * | 2004-10-22 | 2006-04-27 | Instytut Farmaceutyczny | Salt of montelukast with tert.-butylamine |
WO2007005965A1 (en) * | 2005-07-05 | 2007-01-11 | Teva Paharmaceutical Industries Ltd. | Purification of montelukast |
-
2007
- 2007-10-19 WO PCT/IN2007/000492 patent/WO2009027990A1/en active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995018107A1 (en) * | 1993-12-28 | 1995-07-06 | Merck & Co., Inc. | Process for the preparation of leukotriene antagonists |
US20050234241A1 (en) * | 2004-04-15 | 2005-10-20 | Venkataraman Sundaram | Process for the preparation of [R-(E)-1-[[[1-[3-[2-[7-chloro-2-quinolinyl]ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (montelukast) and its pharmaceutically acceptable salts |
WO2006008751A2 (en) * | 2004-07-19 | 2006-01-26 | Matrix Laboratories Ltd | Process for the preparation of montelukast and its salts |
WO2006043846A1 (en) * | 2004-10-22 | 2006-04-27 | Instytut Farmaceutyczny | Salt of montelukast with tert.-butylamine |
WO2007005965A1 (en) * | 2005-07-05 | 2007-01-11 | Teva Paharmaceutical Industries Ltd. | Purification of montelukast |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011121091A1 (en) | 2010-03-31 | 2011-10-06 | Krka, D.D., Novo Mesto | Efficient synthesis for the preparation of montelukast and novel crystalline form of intermediates therein |
WO2012015255A3 (en) * | 2010-07-30 | 2012-04-26 | Dong Kook Pharm. Co., Ltd | Novel montelukast 4-halobenzylamine salt and method for preparing montelukast sodium salt by using the same |
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