WO2009007987A1 - An improved process for the preparation of alfuzosin and its novel polymorph - Google Patents
An improved process for the preparation of alfuzosin and its novel polymorph Download PDFInfo
- Publication number
- WO2009007987A1 WO2009007987A1 PCT/IN2007/000379 IN2007000379W WO2009007987A1 WO 2009007987 A1 WO2009007987 A1 WO 2009007987A1 IN 2007000379 W IN2007000379 W IN 2007000379W WO 2009007987 A1 WO2009007987 A1 WO 2009007987A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alfuzosin
- formula
- acid
- solvent
- amorphous
- Prior art date
Links
- 0 CN(CCCNC(C1OCCC1)=O)c1nc(*)c(cc(c(OC)c2)OC)c2n1 Chemical compound CN(CCCNC(C1OCCC1)=O)c1nc(*)c(cc(c(OC)c2)OC)c2n1 0.000 description 3
- WNMJYKCGWZFFKR-UHFFFAOYSA-N CN(CCCNC(C1OCCC1)=O)c1nc(N)c(cc(c(OC)c2)OC)c2n1 Chemical compound CN(CCCNC(C1OCCC1)=O)c1nc(N)c(cc(c(OC)c2)OC)c2n1 WNMJYKCGWZFFKR-UHFFFAOYSA-N 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
Definitions
- the present invention relates to an improved process for the preparation of Alfuzosin of formula (I).
- the process involves utilizing intermediate of formula (Ia) wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p-toluene sulfonic acid and the like.
- S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p-toluene sulfonic acid and the like.
- the present invention also relates to novel Amorphous form of Alfuzosin of formula (I).
- Alfuzosin Hydrochloride is prescribed for treatment of symptoms associated with benign prostatic hyperplasia (BPH) such as urinary frequency, nocturia, weak stream, hesitancy and incomplete emptying. It is chemically known as (R,S)-N-[3-[(4-ammo-6,7-dimethoxy-2- quinazolinyl)methylamino] propyl] tetrahydro-2-furancarboxamide hydrochloride. It functions as an antagonist of ⁇ i-arenergic receptor, and is useful as antihypertensive agent and dysuria curing agent. Alfuzosin is first disclosed in U.S. patent no. 4,315,007. The process for the preparation of Alfuzosin as disclosed in the patent is described in synthetic diagram as shown is Scheme-I and Scheme-II.
- Scheme-II The process for preparation of Alfuzosin of formula (I) as disclosed in Scheme-II involves condensation of compound of formula (II) with compound of formula (VI) in the presence of tetrahydrofuran and carbonyl diimidazole at reflux temperature to obtain Alfuzosin of formula (I).
- Alfuzosin obtained by this process contains many impurities, and thus obtained in form of oily residue. Also the overall yield of this reaction is low.
- WO 2006030449 discloses crystalline Alfuzosin base with characteristic XRD pattern.
- WO 2006090268 discloses crystalline Form A of Alfuzosin.
- US 20070105880 disclose solid form of Alfuzosin base. This patent however does not disclose any polymorphic details of Alfuzosin base.
- GB 2231571, CN 1616438, US 20070066824 and WO 2007063556 are other patents and/or patent applications which discloses process for the preparation of Alfuzosin and pharmaceutically acceptable salts thereof.
- Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes in solid state.
- the polymorphic and pseudopolymorphic solids display different physical properties, including those due to packing, and various thermodynamic, spectroscopic, interfacial and mechanical properties (See H. Brittain, Polymorphism in Pharmaceutical Solids, Marcel Dekker, New York, N. Y., 1999, pp. 1-2). It is known that the amorphous form of an individual pharmaceutical active substance has different dissolution characteristics and a different bioavailability in comparison to crystalline forms (Konno T., Chem. Pharm. Bull, 1990, 38:2003-2007). It is generally known that pharmaceutical active substances in amorphous form are better soluble, or dissolve more quickly than crystalline ones.
- the primary object of the present invention is to provide an improved process for the preparation of Alfuzosin of formula (I) and optionally converting it into its hydrochloride salt
- Another object of the present invention is to provide an improved process for the preparation of Alfuzosin of formula (I) which utilises compound of formula (Ia) and optionally converting it into its hydrochloride salt
- Yet another object of the present invention is to provide a process for preparation of compound of formula (Ia) .
- Further object of the present invention is to provide novel amorphous form of Alfuzosin of Formula (I) and its process for preparation
- the present invention provides novel Amorphous form of Alfuzosin of formula (I).
- Another aspect of the present invention provides a process for the preparation of Alfuzosin of formula (I) comprising steps of, (a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent,
- Yet another aspect of the present invention provides a process for the preparation of Amorphous Alfuzosin comprising steps of
- Still further aspect of the present invention provides a process for the preparation of compound of formula (Ia) comprising of treating Amorphous Alfuzosin with organic acid in the presence of solvent.
- Yet further aspect of the present invention provides another process for the preparation of Amorphous Alfuzosin comprising of treating compound of formula (Ia) with base in the presence of solvent to obtain Amorphous Alfuzosin.
- Fig-1 represents PXRD of amorphous form Alfuzosin. Detailed description of the invention
- one embodiment provides an improved process for the preparation of Alfuzosin of formula (I) as shown in the synthetic representation given in Scheme-Ill.
- Another embodiment of the present invention provides a process for the preparation of Amorphous Alfuzosin comprising steps of, (a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent,
- the compound of formula (II) is reacted, with tetrahydrofuoic acid in presence of solvent and an activating agent.
- the solvent can be selected from methelenedichloride, dimethylformamide, dimethylacetamide or dimethylsulphoxide and the like or mixtures thereof.
- the activating agent can be selected from carbonyl diimidazole or thionyl chloride and the like.
- reaction mixture After completion of the reaction the reaction mixture is cooled and filtered. Further the filtrate is treated with aqueous basic solution of sodium hydroxide or any equivalent thereof and the layers are separated. The solvent is distilled off to obtain Amorphous Alfuzosin base.
- Yet another process for obtaining Amorphous Alfuzosin comprises of dissolving Alfuzosin base obtained by any method know perse; in solvent to obtain a solution.
- the said solvent comprises of ethylenedichlori.de, acetone, methanol, chloroform and the like.
- the solvent is distilled off to obtain Amorphous Alfuzosin.
- Amorphous Alfuzosin base thus obtained is converted to compound of formula (Ia) by treatment with organic acid in the presence of solvent.
- Organic acid can be selected from acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p-toluene sulfonic acid and the like.
- the solvent can be selected from acetonitrile, isopropyl alcohol, acetone, ethyl acetate, methelenedichloride and the like or mixtures thereof.
- the reaction can be carried out at room temperature or at reflux temperature of the solvent.
- the acid addition salts thus obtained can be further purified by carrying out leaching in solvents such as acetontirile, methanol, ethyl acetate, acetone and the like. Leaching can be carried out at room temperature or at reflux temperature of the solvent.
- Intermediate of formula (Ia) can be optionally converted to Alfuzosin hydrochloride by dissolving in an alcohol and treating it with alcoholic hydrochloric acid.
- compound of formula (Ia) can be directly treated with alcoholic hydrochloric acid to obtain Alfuzosin hydrochloride.
- Alcohol can be selected from methanol, ethanol, 2-propanol, isopropanol and the like or mixtures thereof.
- compound of formula (Ia) obtained by the process of present invention can be further converted to Amorphous Alfuzosin base by treatment with base in the presence of solvent.
- Base can be selected from group comprising of alkali or alkaline metal hydroxides like sodium or potassium hydroxide.
- Solvent can be selected from chlorinated hydrocarbon e.g. methelenedichloride, ethelenedichloride, chloroform and the like. The organic layer is separated from aqueous layer and solvent is distilled off to obtain Amorphous Alfuzosin base.
- Example 2 Preparation of Alfuzosin acid addition salt To Amorphous Alfuzosin obtained in example 1 is added methylenedichloride and acetic acid. The mixture was heated to reflux temperature. After the completion of the reaction, it is cooled and filtered the crystals are filtered, washed and dried to obtain salt. (HPLC: >98%)
- acid addition salts like oxalic acid, succinic acid, methane sulfonic acid and p-toluene sulfonic acid salts can be prepared in similar manner by addition of corresponding organic acid to Amorphous Alfuzosin.
- Example 5 Preparation of Alfuzosin hydrochloride To the Amorphous Alfuzosin obtained in example 1 was added calculated amount of IPA- HCl and heated to get clear solution. Charcoal was added and filtered it form hyflo bed. The reaction mixture was cooled and the crystals were filtered under nitrogen atmosphere and dried to obtain Alfuzosin hydrochloride.
- Example 6 Preparation of Amorphous Alfuzosin
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to an improved process for the preparation of Alfuzosin of formula (I). The process involves utilizing intermediate of formula (Ia) wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p-toluene sulfonic acid and the like. The present invention also relates to novel Amorphous form of Alfuzosin of formula (I).
Description
AN IMPROVED PROCESS FOR THE PREPARATION OF ALFUZOSIN AND ITS NOVEL POLYMORPH.
Field of the Invention
The present invention relates to an improved process for the preparation of Alfuzosin of formula (I). The process involves utilizing intermediate of formula (Ia) wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p-toluene sulfonic acid and the like. The present invention also relates to novel Amorphous form of Alfuzosin of formula (I).
Background of the Invention
Alfuzosin Hydrochloride is prescribed for treatment of symptoms associated with benign prostatic hyperplasia (BPH) such as urinary frequency, nocturia, weak stream, hesitancy and incomplete emptying. It is chemically known as (R,S)-N-[3-[(4-ammo-6,7-dimethoxy-2- quinazolinyl)methylamino] propyl] tetrahydro-2-furancarboxamide hydrochloride. It functions as an antagonist of αi-arenergic receptor, and is useful as antihypertensive agent and dysuria curing agent.
Alfuzosin is first disclosed in U.S. patent no. 4,315,007. The process for the preparation of Alfuzosin as disclosed in the patent is described in synthetic diagram as shown is Scheme-I and Scheme-II.
Scheme-I
Scheme-II
The process for preparation of Alfuzosin of formula (I) as disclosed in Scheme-II involves condensation of compound of formula (II) with compound of formula (VI) in the presence of tetrahydrofuran and carbonyl diimidazole at reflux temperature to obtain Alfuzosin of formula (I). Alfuzosin obtained by this process contains many impurities, and thus obtained in form of oily residue. Also the overall yield of this reaction is low.
The prior art discloses crystalline and solid forms of Alfuzosin base. WO 2006030449 discloses crystalline Alfuzosin base with characteristic XRD pattern. WO 2006090268 discloses crystalline Form A of Alfuzosin. US 20070105880 disclose solid form of Alfuzosin base. This patent however does not disclose any polymorphic details of Alfuzosin base.
GB 2231571, CN 1616438, US 20070066824 and WO 2007063556 are other patents and/or patent applications which discloses process for the preparation of Alfuzosin and pharmaceutically acceptable salts thereof.
Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes in solid state. The polymorphic and pseudopolymorphic solids display different physical properties, including those due to packing, and various thermodynamic, spectroscopic, interfacial and mechanical properties (See H. Brittain, Polymorphism in Pharmaceutical Solids, Marcel Dekker, New York, N. Y., 1999, pp. 1-2). It is known that the amorphous form of an individual pharmaceutical active substance has different dissolution characteristics and a different bioavailability in comparison to crystalline forms (Konno T., Chem. Pharm. Bull, 1990, 38:2003-2007). It is generally known that pharmaceutical active substances in amorphous form are better soluble, or dissolve more quickly than crystalline ones.
Unexpectedly the present inventors have found that Alfuzosin exists in amorphous form. They have also observed that Alfuzosin can be obtained in high purity and yield by utilizing intermediate of formula (Ia).
Object of the invention
The primary object of the present invention is to provide an improved process for the preparation of Alfuzosin of formula (I) and optionally converting it into its hydrochloride salt
Another object of the present invention is to provide an improved process for the preparation of Alfuzosin of formula (I) which utilises compound of formula (Ia) and optionally converting it into its hydrochloride salt
Yet another object of the present invention is to provide a process for preparation of compound of formula (Ia) .
Further object of the present invention is to provide novel amorphous form of Alfuzosin of Formula (I) and its process for preparation
Summary of the invention
The present invention provides novel Amorphous form of Alfuzosin of formula (I).
Another aspect of the present invention provides a process for the preparation of Alfuzosin of formula (I) comprising steps of, (a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent,
(b) distilling off the solvent from the reaction mixture to obtain Amorphous Alfuzosin of formula (I),
(c) treating Amorphous Alfuzosin of formula (I) with organic acid in the presence of solvent to obtain compound of formula (Ia), wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p- toluene sulfonic acid and the like,
(d) optionally treating compound of formula (Ia) with alcoholic hydrochloric acid to
(I obtain Alfuzosin hydrochloride or
(e) treating compound of formula (Ia) with a base in the presence of solvent to obtain Amorphous Alfuzosin,
(f) separating the organic layer and distilling off the solvent to obtain Amorphous Alfuzosin.
Yet another aspect of the present invention provides a process for the preparation of Amorphous Alfuzosin comprising steps of
(a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent, (b) distilling off the solvent from the reaction mixture to obtain Amorphous Alfuzosin.
Further aspect of the present invention provides another process for the preparation of Amorphous Alfuzosin comprising steps of,
(g) dissolving Alfuzosin of formula (I) in a solvent to obtain a solution, (h) distilling off the solvent from said solution to obtain Amorphous Alfuzosin.
Still further aspect of the present invention provides a process for the preparation of compound of formula (Ia) comprising of treating Amorphous Alfuzosin with organic acid in the presence of solvent.
Yet further aspect of the present invention provides another process for the preparation of Amorphous Alfuzosin comprising of treating compound of formula (Ia) with base in the presence of solvent to obtain Amorphous Alfuzosin.
Brief description of the drawings
Fig-1 represents PXRD of amorphous form Alfuzosin.
Detailed description of the invention
In accordance with the object of the present invention one embodiment provides an improved process for the preparation of Alfuzosin of formula (I) as shown in the synthetic representation given in Scheme-Ill.
Scheme-Ill
The present invention provides a process for the preparation of Alfuzosin of formula (I) comprising steps of,
(a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent, (b) distilling off the solvent from the reaction mixture to obtain Amorphous Alfuzosin of formula (I),
(c) treating Amorphous Alfuzosin of formula (I) with organic acid in the presence of solvent to obtain compound of formula (Ia), wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p- toluene sulfonic acid and the like,
(d) optionally treating compound of formula (Ia) with alcoholic hydrochloric acid to obtain Alfuzosin hydrochloride or
(e) treating compound of formula (Ia) with a base in the presence of solvent to obtain Amorphous Alfuzosin, (f) separating the organic layer and distilling off the solvent to obtain Amorphous
Alfuzosin.
Another embodiment of the present invention provides a process for the preparation of Amorphous Alfuzosin comprising steps of, (a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent,
(b) distilling off the solvent from the reaction mixture to obtain Amorphous Alfuzosin.
Yet another embodiment of the present invention provides a process for the preparation of compound of formula (Ia) comprising of treating Amorphous Alfuzosin with organic acid in the presence of solvent.
Further embodiment of the present invention provides a process for the preparation of Amorphous Alfuzosin comprising of treating compound of formula (Ia) with base in presence of solvent to obtain Amorphous Alfuzosin.
The compound of formula (II) is reacted, with tetrahydrofuoic acid in presence of solvent and an activating agent. The solvent can be selected from methelenedichloride, dimethylformamide, dimethylacetamide or dimethylsulphoxide and the like or mixtures thereof. The activating agent can be selected from carbonyl diimidazole or thionyl chloride and the like.
After completion of the reaction the reaction mixture is cooled and filtered. Further the filtrate is treated with aqueous basic solution of sodium hydroxide or any equivalent thereof and the layers are separated. The solvent is distilled off to obtain Amorphous Alfuzosin base.
Yet another process for obtaining Amorphous Alfuzosin comprises of dissolving Alfuzosin base obtained by any method know perse; in solvent to obtain a solution. The said solvent comprises of ethylenedichlori.de, acetone, methanol, chloroform and the like. The solvent is distilled off to obtain Amorphous Alfuzosin.
Amorphous Alfuzosin base thus obtained is converted to compound of formula (Ia) by treatment with organic acid in the presence of solvent. Organic acid can be selected from acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p-toluene sulfonic acid and the like. The solvent can be selected from acetonitrile, isopropyl alcohol, acetone, ethyl acetate, methelenedichloride and the like or mixtures thereof.
The reaction can be carried out at room temperature or at reflux temperature of the solvent.
The acid addition salts thus obtained can be further purified by carrying out leaching in solvents such as acetontirile, methanol, ethyl acetate, acetone and the like. Leaching can be carried out at room temperature or at reflux temperature of the solvent.
Intermediate of formula (Ia) can be optionally converted to Alfuzosin hydrochloride by dissolving in an alcohol and treating it with alcoholic hydrochloric acid. Alternatively compound of formula (Ia) can be directly treated with alcoholic hydrochloric acid to obtain Alfuzosin hydrochloride. Alcohol can be selected from methanol, ethanol, 2-propanol, isopropanol and the like or mixtures thereof.
Also compound of formula (Ia) obtained by the process of present invention can be further converted to Amorphous Alfuzosin base by treatment with base in the presence of solvent. Base can be selected from group comprising of alkali or alkaline metal hydroxides like sodium or potassium hydroxide. Solvent can be selected from chlorinated hydrocarbon e.g. methelenedichloride, ethelenedichloride, chloroform and the like. The organic layer is separated from aqueous layer and solvent is distilled off to obtain Amorphous Alfuzosin base.
The process of the present invention is described by the following examples, which are illustrative only and should not be construed so as to limit the scope of the invention in any manner.
Example 1: Preparation of Amorphous Alfuzosin
To 88 ml methylenedichloride was added 24.5 g carbonyl diimidazole and 17.53 g tetrahydrofuroic acid. The reaction mass was stirred for 30 min. at 10-150C and then refluxed for one hr. To it was added 22 g N1-(4-amino-6,7-dimethoxyquinazol-2-yl)-N1- methylpropylenediamine in 66 ml dichloromethane at 38-400C. The reaction mixture was monitored by TLC. The reaction mixture was cooled and filtered through hyflo bed. 110 ml of water was added and pH adjusted to 10- 12 by using 2N NaOH solution. Organic layer was
separated, washed with water and then brine. The solvent was distilled off to obtain Amorphous Alfuzosin.
Example 2: Preparation of Alfuzosin acid addition salt To Amorphous Alfuzosin obtained in example 1 is added methylenedichloride and acetic acid. The mixture was heated to reflux temperature. After the completion of the reaction, it is cooled and filtered the crystals are filtered, washed and dried to obtain salt. (HPLC: >98%)
Other acid addition salts like oxalic acid, succinic acid, methane sulfonic acid and p-toluene sulfonic acid salts can be prepared in similar manner by addition of corresponding organic acid to Amorphous Alfuzosin.
Example 3: Purification of acid addition salts of alfuzosin
To the salts obtained in example 2 was added acetontirile. It is heated to reflux for few hours and the crystals are filtered off. Further the crystals are washed and dried to get desired salts. (HPLC: >99.5%)
Example 4: Preparation of Alfuzosin hydrochloride
To the salts obtained in example 3 was added isopropyl alcohol and IPA-HCl (10 %) till acidic pH. Further the reaction mixture was heated to reflux for few hours and cooled to room temperature. The crystals are filtered off under nitrogen atmosphere, washed with isopropyl alcohol and dried to obtain Alfuzosin hydrochloride.
Example 5: Preparation of Alfuzosin hydrochloride To the Amorphous Alfuzosin obtained in example 1 was added calculated amount of IPA- HCl and heated to get clear solution. Charcoal was added and filtered it form hyflo bed. The reaction mixture was cooled and the crystals were filtered under nitrogen atmosphere and dried to obtain Alfuzosin hydrochloride.
Example 6: Preparation of Amorphous Alfuzosin
To the salts obtained in example 3 was added methylenedichloride and water. pH was adjusted to 10-12 by using 2N NaOH. The layers were separate and organic layer was washed with water and then brine. The solvent was distilled off to obtain Amorphous Alfuzosin.
Claims
1. Amorphous Alfuzosin base.
2. Amorphous Alfuzosin base characterized by powder x-ray diffraction spectrum which is substantially the same as shown in Fig-1.
3. A process for the preparation of Alfuzosin of formula (I) comprising steps of,
(a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent,
(b) distilling off the solvent from the reaction mixture to obtain Amorphous Alfuzosin of formula (I),
(c) treating Amorphous Alfuzosin of formula (I) with organic acid in the presence of solvent to obtain compound of formula (Ia), wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid and p-toluene sulfonic acid,
(d) optionally treating compound of formula (Ia) with alcoholic hydrochloric acid to obtain Alfuzosin hydrochloride or
(f) separating the organic layer and distilling off the solvent to obtain Amorphous Alfuzosin.
4. A process for the preparation of Amorphous Alfuzosin comprising steps of, (a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI) in the presence of solvent,
(b) distilling off the solvent from the reaction mixture to obtain Amorphous Alfuzosin.
5. A process for the preparation of compound of formula (Ia), wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid and p-toluene sulfonic acid comprising of treating Amorphous Alfuzosin with organic acid in the presence of solvent.
6. A process for the preparation of Alfuzosin hydrochloride comprising of treating compound of formula (Ia) with alcoholic hydrochloric acid.
(a) condensing compound of formula (II) with tetrahydrofuroic acid of formula (VI)
(b) distilling off the solvent from the reaction mixture to obtain Amorphous Alfuzosin of formula (I),
(c) treating Amorphous Alfuzosin of formula (I) with organic acid in the presence of solvent to obtain compound of formula (Ia), wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid and p-toluene sulfonic acid,
8. A process for the preparation of Amorphous Alfuzosin comprising steps of, (e) treating compound of formula (Ia) with base in the presence of solvent,
(f) separating the organic layer and distilling off the solvent to obtain Amorphous Alfuzosin.
9. A process as claimed in claims 3, 4 and 7, wherein said solvent in step (a) is selected from methelenedichloride, dimethylformamide, dimethylacetamide and dimethylsulphoxide.
10. A process as claimed in claims 3 step (c), 5 and 7 step (c), wherein said organic acid is selected from acetic acid, oxalic acid, succinic acid, methane sulfonic acid and p- toluene sulfonic acid.
11. A process as claimed in claims 3 step (c), 5 and 7 step (c), wherein said solvent is selected from acetonitrile, isopropyl alcohol, acetone, ethyl acetate and methelenedichloride.
12. A process as claimed in claim 10, wherein compound of formula (Ia) is further purified by carrying out leaching in solvents selected from acetontirile, methanol, ethyl acetate and acetone.
13. A process as claimed in claims 3 step (d), 6 and 7 step (d),, wherein said alcohol is selected from methanol, ethanol, 2-propanol and isopropanol or mixtures thereof.
14. A process as claimed in claim 3 and 8, wherein said solvent in step (e) is selected from methelenedichloride, ethelenedichloride and chloroform.
15. A process as claimed in claim 3 and 8, wherein said base in step (e) is sodium hydroxide.
16. A process for the preparation of Amorphous Alfuzosin comprising steps of, (g) dissolving Alfuzosin of formula (I) in a solvent to obtain a solution, (h) distilling off the solvent from said solution to obtain Amorphous Alfuzosin.
17. A process as claimed in claim 16, wherein said solvent in step (g) is selected from ethylenedichloride, acetone, methanol and chloroform.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1330/MUM/2007 | 2007-07-11 | ||
IN1330MU2007 IN2007MU01330A (en) | 2005-03-04 | 2007-08-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2009007987A1 true WO2009007987A1 (en) | 2009-01-15 |
Family
ID=39493896
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2007/000379 WO2009007987A1 (en) | 2007-07-11 | 2007-08-30 | An improved process for the preparation of alfuzosin and its novel polymorph |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2009007987A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITPD20080215A1 (en) * | 2008-07-21 | 2010-01-22 | Lundbeck Pharmaceuticals Italy Spa | METHOD OF PREPARATION OF ALPHUZOSIN CHLORIDRATE ANHYDROUS |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4315007A (en) * | 1978-02-06 | 1982-02-09 | Synthelabo | 4-Amino-6,7-dimethoxyquinazol-2-yl alkylenediamines |
WO2006090268A2 (en) * | 2005-02-28 | 2006-08-31 | Glenmark Pharmaceuticals Limited | Processes for the preparation of alfuzosin and salts thereof and novel crystalline forms of alfuzosin |
US20070105880A1 (en) * | 2005-11-08 | 2007-05-10 | Torrent Pharmaceuticals Limited | Process for the preparation of alfuzosin |
-
2007
- 2007-08-30 WO PCT/IN2007/000379 patent/WO2009007987A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4315007A (en) * | 1978-02-06 | 1982-02-09 | Synthelabo | 4-Amino-6,7-dimethoxyquinazol-2-yl alkylenediamines |
WO2006090268A2 (en) * | 2005-02-28 | 2006-08-31 | Glenmark Pharmaceuticals Limited | Processes for the preparation of alfuzosin and salts thereof and novel crystalline forms of alfuzosin |
US20070105880A1 (en) * | 2005-11-08 | 2007-05-10 | Torrent Pharmaceuticals Limited | Process for the preparation of alfuzosin |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITPD20080215A1 (en) * | 2008-07-21 | 2010-01-22 | Lundbeck Pharmaceuticals Italy Spa | METHOD OF PREPARATION OF ALPHUZOSIN CHLORIDRATE ANHYDROUS |
WO2010010058A1 (en) * | 2008-07-21 | 2010-01-28 | Lundbeck Pharmaceuticals Italy S.P.A. | Method of preparing anhydrous alfusozin hydrochloride |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5632279B2 (en) | Preparation method and polymorph of ivabradine hydrochloride | |
JP5833626B2 (en) | Preparation process and intermediate of lapatinib | |
US20070027170A1 (en) | Process for preparing amino crotonyl compounds | |
WO2015166379A2 (en) | Novel polymorphic forms of vortioxetine and its pharmaceutically acceptable salts | |
HUE031029T2 (en) | Method for producing substituted (z)-alpha-fluoro-beta-amino-acrylaldehydes | |
EP2794610B1 (en) | Processes and intermediates for preparing pralatrexate | |
EP3022209B1 (en) | Dolutegravir potassium salt | |
EP2539321A1 (en) | Saxagliptin intermediates, saxagliptin polymorphs, and processes for preparation thereof | |
JP2008515840A (en) | Semi-synthetic method for the preparation of 10-deacetyl-N-debenzoyl-paclitaxel | |
WO2016200930A1 (en) | Methods of making protein deacetylase inhibitors | |
CN112851646A (en) | Preparation method of Tegolrazan | |
WO2012061469A2 (en) | Crystalline forms of pralatrexate | |
WO2019008520A1 (en) | A process for preparing alectinib or a pharmaceutically acceptable salt thereof | |
US20070100143A1 (en) | Crystalline alfuzosin base | |
WO2020051014A1 (en) | Processes for the preparation of tenapanor and intermediates thereof | |
WO2009007987A1 (en) | An improved process for the preparation of alfuzosin and its novel polymorph | |
WO2019048974A1 (en) | Process for the preparation of nintedanib | |
US8093384B2 (en) | Processes for the preparation of alfuzosin | |
JP7379381B2 (en) | Intermediates and processes for the manufacture of linagliptin and its salts | |
WO2008038143A2 (en) | Novel solid forms of rimonabant and synthetic processes for their preparation | |
US10927121B1 (en) | Technologies for removing residual solvent from nalmefene hydrochloride and producing crystalline nalmefene hydrochloride monohydrate, monosolvate, or crystalline nalmefene hydrochloride dihydrate | |
JP5234856B2 (en) | Crystal of compound having NPYY5 receptor antagonistic action | |
JP2009526030A (en) | CABERGOLINE AND METHOD FOR PRODUCING NOVEL POLYMORPHIM FORM | |
WO2009001369A1 (en) | An improved process for the preparation of alfuzosin hydrochloride | |
JP2007517028A (en) | Amorphous (4R-cis) -6- [2- [3-phenyl-4- (phenylcarbamoyl) -2- (4-fluorophenyl) -5- (1-methylethyl) -pyrrol-1-yl ] -Ethyl] -2,2-dimethyl- [1,3] -dioxan-4-yl-acetic acid |
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: 07866690 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: 07866690 Country of ref document: EP Kind code of ref document: A1 |