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A Process For&Nbsp;Making Imatinib And Its Novel Intermediates Thereof

Abstract: ABSTRACT The present invention relates to a novel process of preparation of an anticancer drug and its novel intermediates. More specifically, the present invention relates to a process for preparation of    4-(4-Methyl-piperazin-l-ylmethy!)-N-{4-methyl-3-[(4-pyridin-3- yl)pyrimidin-2-ylamino]-pbenyl}-benzamide and its novel intermediates.

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Patent Information

Application #
Filing Date
25 February 2009
Publication Number
34/2009
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
Parent Application

Applicants

AVRA LABORATORIES PVT. LTD
AVRA HOUSE, 7-102/54 SAI ENCLAVE, HABSHIGUDA, HYDERABAD-500 007

Inventors

1. RAO, RAMAKRISHNA
AVRA HOUSE, 7-102/54 SAI ENCLAVE, HABSHIGUDA, HYDERABAD-500 007
2. ALLA, VENKATA RAMA RAO
AVRA HOUSE, 7-102/54 SAI ENCLAVE, HABSHIGUDA, HYDERABAD-500 007
3. SINGH, KUMAR ALOK
AVRA HOUSE, 7-102/54 SAI ENCLAVE, HABSHIGUDA, HYDERABAD-500 007
4. CHITLURI, SUMANTH
AVRA HOUSE, 7-102/54 SAI ENCLAVE, HABSHIGUDA, HYDERABAD-500 007

Specification

FIELD OF THE INVENTION The present invention relates to a novel process of preparation of an anticancer drug and its novel intermediates. More specifically, the present invention relates to a process for preparation of 4-(4-Methyl-piperazin-l-ylmethyl)-N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidin-2-ylamino]-phenyl}-benzamide and its novel intermediates. BACKGROUND OF THE INVENTION Imatinib (4-{4-Methyl-piperazin-l-ylmethyl)-N-{4-methyI-3-[(4-pyridin-3-yl)pyrimidin-2-ylamino]-phenyl}-benzamide) is known as inhibitor of tyrosine kinases and is indicated for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GlSTs). Synthesis of Imatinib (4-(4-Methyl-piperazin-l-ylmethyl)-N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidin-2-ylamino]-phenyl}-benzamide) is reported in EP 564409 (Zimmerman). However this synthesis involved virulent cyanamide and also the use of sodium metal. WO 03/066613, WO 04/ 108699 and Szakacs et all J. Med.Chem 2005, 48, 249 teaches procedure of synthesizing Imatinib. But all these methods use the toxic, hazardous reagent cyanamide. Yi-Feng Liu et al J.Process Organic Reasearch and Development Vol 12, No3, 2008 pp 490-495 teaches a method of preparation of Imatinib which uses copper salts for the C-N bond forming reaction. But this method also uses highly toxic and unstable hydrazine for the reduction of the intermediate nitro compounds. Therefore, there is clearly a need to develop a new process for the preparation of imatinib that overcomes the shortcomings of the prior art. OBJECTS OF THE INVENTION It is an object of the invention to develop a novel method of preparing imatinib and its pharmaceutically acceptable salts. It is another important object of the invention to develop an efficient, safe and simple process for making imatinib. It is yet another important object of the invention to develop novel and viable intermediates useful in the preparation of imatinib. SUMMARY OF THE INVENTION Accordingly, to meet the stated objectives and to overcome the disadvantages of the prior art, the present invention discloses a process of making imatinib, a compound (j) of the formula DETAILED DESCRIPTION OF THE INVENTION This invention describes a novel process of preparation of 4-(4-Methyl-piperazin-l-ylmethyl)-N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidin-2-yiamino]-phenyl}-benzamide. The summary of general process of the present invention is as follows: chlorinating 4-{MethGxymethyl)benzoic acid to yield 4-(Methoxymethyl)benzoyl chloride(b); reacting the product obtained from the preceding step with 3-bromo-4-methyl aniline to yield give N-(3-bromo-4-methylphenyl)-4-

Documents

Application Documents

# Name Date
1 400-CHE-2009 POWER OF ATTORNEY 08-04-2009.pdf 2009-04-08
1 400-CHE-2009_EXAMREPORT.pdf 2016-07-02
2 400-che-2009 form-9-30-06-2009.pdf 2009-06-30
2 400-che-2009 abstract.pdf 2011-09-02
3 400-che-2009 form-18-30-06-2009.pdf 2009-06-30
3 400-che-2009 claims.pdf 2011-09-02
4 400-che-2009 correspondence others.pdf 2011-09-02
4 400-che-2009 correspondence others-30-06-2009.pdf 2009-06-30
5 400-che-2009 correspondence-others.pdf 2011-09-02
5 400-che-2009 form-3.pdf 2011-09-02
6 400-che-2009 description (complete).pdf 2011-09-02
6 400-che-2009 form-1.pdf 2011-09-02
7 400-che-2009 description (complete).pdf 2011-09-02
7 400-che-2009 form-1.pdf 2011-09-02
8 400-che-2009 correspondence-others.pdf 2011-09-02
8 400-che-2009 form-3.pdf 2011-09-02
9 400-che-2009 correspondence others-30-06-2009.pdf 2009-06-30
9 400-che-2009 correspondence others.pdf 2011-09-02
10 400-che-2009 form-18-30-06-2009.pdf 2009-06-30
10 400-che-2009 claims.pdf 2011-09-02
11 400-che-2009 form-9-30-06-2009.pdf 2009-06-30
11 400-che-2009 abstract.pdf 2011-09-02
12 400-CHE-2009_EXAMREPORT.pdf 2016-07-02
12 400-CHE-2009 POWER OF ATTORNEY 08-04-2009.pdf 2009-04-08