Title of Invention | PROCESS FOR THE PREPARATION OF NOVEL INTERMEDIATES USEFUL IN THE SYNTHESIS OF TAMSULOSIN HYDROCHLORIDE |
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Abstract | The present invention provides process for the preparation of 1-(2- (arylmethoxy)ethyl)-IH-tetrazole-5-thiols of the formula (I), N-N ~ ',...HS N"N j~;(:1 ~~ .': 6H,CH,-O-CH, ~R, R, .'1;::; (I) wherein R1, R2, RJ are same or different and independently represent hydrogen, (C1-C4)alkoxy, aryl(C1-C4)alkoxy or substituted aryl(C1-C4)alkoxy group; aryl "C' group represents five or six membered aromatic group. |
Full Text | (IV) converting the Tamsulosin base of the formula-XVIII into Tamsulosin hydrochloride 01 formula-I by conventional methods. The reaction scheme for the preparation of Tamsulosin hydrochloride having the formula-I given above employing the novel intermediate of the formula-Ill of the present invention is shown in the scheme I below The monoalkylation of the primary amine of formula-IV is carried out by the method of Decker & Becker [Decker & Becker, Ann, 395, 328 (1913)]. So far this method has not been used earlier for making Tamsulosin hydrochloride of formula-I. The above mentioned process has been the subject matter of our co pending application no. 599/MAS/ 2002. The main drawbacks in this process are: 1. More number of steps is involved there-by making the route very cumbersome. 2. Highly pyrophoric and expensive reagent lithium aluminium hydride is used to carry out the reduction of amide to secondary amine. Recognizing the importance of Tamsulosin hydrochloride of the formula-I as a widely used drug for the treatment of benign prostate hyperplasia, and taking into account the difficulties of the hitherto known processes for its preparation, we under took research to develop a simple, cheap and commercially viable process for producing Tamsulosin hydrochloride, starting with (R)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide of formula-IV. While doing do we could develop two important and novel intermediates of the formula-II & III as defined above. We have described and claimed the novel Compounds of the formula-II and their process of preparation in our another co pending application no. 598/MAS/2002 and a process for the preparation of Tamsulosin hydrochloride using te novel intermediate of the present invention in our co pending application no. 599/MAS/2002. The main objective of the present invention, therefore, is to provide novel intermediates namely phenyl substituted 2-methoxy-5-(2R)-2 {[(1E/Z-penylmethylene)aminopropyl} benzenesulfonamide of formula-Ill, where R represents H, 4-OCH3, 4-OH or 4-fluoro. Advantages of the invention The novel intermediates of the present invention are very useful for the preparation of Tamsulosin hydrochloride, which is a widely used drug for the treatment of benign prostate hyperplasia. The process of preparing Tamsulosin hydrochloride using the novel intermediate of the present invention is not only simple but also economical yielding Tamsulosin hydrochloride in a highly purified form (99.5%), 2. A process for the preparation of the novel imine compounds, 2-methoxy-5-2(R)-2-{[(l-E/Z- phenylmethylene)amino]propyl} benzenesulfonamide of the formula-Ill as defined in claim 1, which comprises reacting the compound, R(-)-5-[(2-amino-2-methyl)ethyl]-2- methoxybenzenesulfonamide of the formula-IV with a substituted aromatic benzaldehyde of the formula-XVI, where R represents group such as H, 4-OH, 4-OCH3 or 4-fluoro to obtain novel compounds namely phenyl substituted 2-methoxy-5-(2R)-2- {[(1 -E/Z- pheylmethylene)amino] propyl}benzenesulfonamide of formula-Ill, azeotropically removing the water during the reaction using solvents such as toluene, xylene etc or by simultaneous distillation of water formed using an alcholic solvent such as methanol, ethanol, isopropyl alcohol, n-butanol etc. 3. A process as claimed in claim 2 wherein the reaction is effected by azeotropically removing the water using a solvent. 4. A process as claimed in claim 2 wherein the solvent, such as toluene, xylene etc. is used. 5. A process as claimed in claim 1 wherein the reaction is effected by simultaneous distillation of the water formed using an alcoholic solvent such as methanol, ethanol, isopropyl alcohol, n-butanol etc. 6. A process for the preparation of quarternary benzylidene ammonium salts of formula-Ill, 2-methoxy-5-2(R)-2-{[(l-E/Z-phenylmethylene)amino]propyl} benzenesulfonamide as defined in claim 1 substantially as herein described with reference to the Examples, |
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597-mas-2002-claims duplicate.pdf
597-mas-2002-claims original.pdf
597-mas-2002-correspondence others.pdf
597-mas-2002-correspondence po.pdf
597-mas-2002-description complete duplicate.pdf
597-mas-2002-description complete original.pdf
Patent Number | 208037 | ||||||||
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Indian Patent Application Number | 597/MAS/2002 | ||||||||
PG Journal Number | 31/2007 | ||||||||
Publication Date | 03-Aug-2007 | ||||||||
Grant Date | 06-Jul-2007 | ||||||||
Date of Filing | 14-Aug-2002 | ||||||||
Name of Patentee | NATCO PHARMA LIMITED | ||||||||
Applicant Address | NATCO HOUSE,ROADNO.2, BANJARA HILLS , HYDERABAD 500 033. | ||||||||
Inventors:
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PCT International Classification Number | C07C143/80 | ||||||||
PCT International Application Number | N/A | ||||||||
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PCT Conventions:
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