Invention Grant
- Patent Title: Process for preparation of imatinib base
- Patent Title (中): 伊马替尼碱的制备方法
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Application No.: US11813212Application Date: 2005-12-30
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Publication No.: US07674901B2Publication Date: 2010-03-09
- Inventor: Wojciech Szczepek , Wojciech Luniewski , Lukasz Kaczmarek , Bogdan Zagrodzki , Dorota Samson-Lazinska , Wieslaw Szelejewski , Maciej Skarzynski
- Applicant: Wojciech Szczepek , Wojciech Luniewski , Lukasz Kaczmarek , Bogdan Zagrodzki , Dorota Samson-Lazinska , Wieslaw Szelejewski , Maciej Skarzynski
- Applicant Address: PL Warsaw
- Assignee: Instytut Farmaceutyczny
- Current Assignee: Instytut Farmaceutyczny
- Current Assignee Address: PL Warsaw
- Agency: Matthias Scholl, PC
- Agent Matthias Scholl
- Priority: PLP.372016 20041230; PLP.376691 20050819; PLP.377984 20051108
- International Application: PCT/PL2005/000088 WO 20051230
- International Announcement: WO2006/071130 WO 20060706
- Main IPC: C07D419/00
- IPC: C07D419/00

Abstract:
An improved process for the preparation of imatinib base and its pharmaceutically acceptable acid addition salts by (a) reacting 2-methyl-5-nitroaniline with cyanamide in the presence of hydrochloric acid to obtain 1-(2-methyl-5-nitrophenyl)guanidine hydrochloride; (b) converting 1-(2-methyl-5-nitrophenyl)guanidine hydrochloride to 1-(2-methyl-5-nitrophenyl)guanidine nitrate; (c) condensing 3-acetylpyridine with N,N-dimethylformamide dimethyl acetal to obtain 3-(dimethylamino)-1-(3-pyridinyl)-prop-2-en-1-one; (d) reacting 3-(dimethylamino)-1-(3-pyridinyl)-prop-2-en-1-one with 1-(2-methyl-5-nitrophenyl)guanidine nitrate to obtain N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine; (e) reducing N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine using hydrazine in the presence of Raney nickel to obtain N-(5-amino-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidine-amine; (f) condensing N-(5-amino-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidine-amine with 4-chloromethylbenzoyl chloride in the presence of an inorganic base to obtain 4-(chloromethyl)-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide; and (g) condensing 4-(chloromethyl)-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide with an excess of N-methylpiperazine to obtain imatinib base; and adding water or a mixture of water and an organic solvent; and isolating said imatinib base. The process allows for using simple starting materials, while simultaneously avoiding a laborious isolation and purification of intermediates and the final product, thereby facilitating scale-up.
Public/Granted literature
- US20080194819A1 Process For Preparation of Imatinib Base Public/Granted day:2008-08-14
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