FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
A PROCESS FOR PURIFICATION OF ALFUZOSIN OR SALT THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra (East),
Mumbai-400 051.
3. PREAMBLE TO THE DESCRIPTION
The present invention relates to a facile process for the purification of alfuzosin hydrochloride
The following specification particularly describes the invention and the manner
in which it is to be performed.
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4. DESCRIPTION
The present invention relates to a facile process for the purification of alfuzosin hydrochloride
Alfuzosin is an alphara1-adenergic blocker indicated for the treatment of benign prostatic hyperplasia (BPH). It is chemically N-[3-[( 4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furan carboxamide of Formula I. It is marketed in the form of its hydrochloride salt for the treatment of BPH.

US Patent number 4,315,007 (the '007 Patent) and Journal of Medicinal Chemistry 29, 19-25 (1986) provides two processes for preparation of alfuzosin or salt thereof. Both the processes either involve high vacuum distillation of intermediates or high-pressure hydrogenation of nitrile intermediate. The anhydrous product obtained by following these processes is usually contaminated with amorphous form and is highly hygroscopic. In addition, the product obtained is not adequately pure for incorporation in to the pharmaceutical dosage forms. Isolation of alfuzosin base and its characterization is also not provided in these references.
British Patent No GB 2231571 (the '571 Patent) provides another process for preparation of alfuzosin, which also involves intermediate of US patent 4,315007, that requires high vacuum distillations. The disclosed method also uses corrosive chemicals such as phosphorous trichloride and phosphorous oxychloride. The yields obtained as per this process are lower and the product purity is not disclosed. The '571 Patent does not provide process for isolation of alfuzosin base or its physical characterization.
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US Patent No 5,545,738 (the 738 Patent) provides processes for preparation of alfuzosin hydrochloride dihydrate from the anhydrous alfuzosin hydrochloride obtained as per the '007 Patent. The 738 Patent do not disclose a process for preparation or isolation of alfuzosin base.
The present inventors have developed an easy process of purification of alfuzosin hydrochloride through methanol solvate formation. The present inventors have found that Alfuzosin hydrochloride obtained by this method has purity of 99% or above when measured by HPLC.
In one of the aspect of the present invention there is provided a process for preparation of alfuzosin hydrochloride wherein the said process comprises of,
a) converting alfuzosin base to alfuzosin hydrochloride alcohol solvate by treating the alfuzosin base crude with alcoholic hydrogen chloride,
b) isolating alcohol solvate of alfuzosin hydrochloride by filtration,
c) refluxing the alcohol solvate of alfuzosin with acetone,
d) isolating alfuzosin hydrochloride from the reaction mass thereof.
Alfuzosin base used as starting material can be prepared by methods known in the art. It is then suspended in an alcoholic solvent and treated with alcoholic hydrogen chloride. The suitable alcohol may be selected from a group comprising one or more of C1-C4 linear chain or branched chain alcohols. The alcohol solvate of alfuzosin hydrochloride is isolated from the reaction mass and refluxed with acetone to free the solvated alcohol. The so obtained alfuzosin hydrochloride has purity of 99% or above.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
EXAMPLE 1
Preparation of Alfuzosin hydrochloride methanol solvate
Alfuzosin base N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl] tetahydro-2-furan carboxamide (73 gm) was suspended in methanol (240 ml) and the pH of the suspension was adjusted between 4 to 6 using methanolic hydrochloric acid.
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The reaction mixture was further stirred at room temperature for 4 hours and filtered.
The wet solid was dried to get title compound.
Yield: 82 gm
HPLC purity: 99.13% by HPLC
EXAMPLE 2 Preparation of Alfuzosin hydrochloride
Alfuzosin hydrochloride methanol solvate (20 gm) was suspended in acetone (400ml).
The reaction mixture was refluxed for 5 hours and then cooled to room temperature.
The obtained solid was filtered and dried to get title compound.
Yield: 17 gm
Purity by HPLC: 99.5%
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WE CLAIM:
1) A process for preparation of alfuzosin hydrochloride wherein the said process
comprises of,
a) converting alfuzosin base to alfuzosin hydrochloride alcohol solvate by treating the alfuzosin base crude with alcoholic hydrogen chloride,
b) isolating alcohol solvate of alfuzosin hydrochloride by filtration,
c) refluxing the alcohol solvate of alfuzosin with acetone,
d) isolating alfuzosin hydrochloride from the reaction mass thereof.

2) A process of claim 1 wherein the alcohol may be selected from a group comprising one or more of C1-C4 linear or branched chain alcohols.
3) A process of claim 2, wherein alcohol used is methanol.