Imatinib mesylate, chemical name: 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide methanesulfonate, molecular formula: C29H31N7O.CH4SO3, molecular weight:589.7, the structural formula is as follows:

Imatinib mesylate, an inhibitor of signal transduction, was developed by Novartis (Switzerland), and was initially marketed in the United States on May 10, 2001. Currently, it has been marketed in more than 60 countries including the United States, the European Union, Japan, and China.
Studies have found that imatinib mesylate can inhibit Bcr-Abl tyrosine kinase at cellular level both in vivo and in vitro, and can selectively inhibit the proliferation of, and induce the apoptosis of cells of Bcr-Abl positive cell lines, as well as fresh cells from patients of Philadelphia chromosome-positive chronic myelocytic leukemia and acute lymphocytic leukemia. In addition, it can also inhibit the tyrosine kinases of the receptor of platelet-derived growth factor (PDGF) and c-Kit, the receptor of stem cell factor (SCF), thus inhibit PDGF- and SCF-mediated cellular events. Imatinib mesylate, which belongs to small-molecule targeted anticancer drug, is suitable for the treatment of patients having chronic myelocytic leukemia (CML) in blast phase, accelerated phase, or in chronic phase after failure of interferon-alpha treatment, as well as patients having unresectable or metastatic malignant gastrointestinal stromal tumors (GIST).
Imatinib and the salt form thereof are first described in U.S. Pat. No. 5,521,184. International Patent Application WO99/03854, WO2005/077933, WO2004/106326, WO2006/054314 and WO2007/023182 have disclosed α, β, α2, H1, I, II, δ, and ε crystal forms of imatinib mesylate. US Patent Application US20060223816 provides a method for preparing α-crystal form of imatinib mesylate, which is stable, well flowable, and suitable for pharmaceutical application. Specifically, mixing the imatinib base with organic solvents, and heating until some of the imatinib base being dissolved in the organic solvents; adding seed crystal of α-crystal form of imatinib mesylate; dissolving methanesulfonic acid in organic solvents, then slowly adding it dropwise into the solution of imatinib base; cooling the reaction liquid to allow the precipitation of imatinib mesylate crystal, separating to obtain the α-crystal form of imatinib mesylate. The organic solvents in this patent application are ketones including butanone and methyl isobutyl ketone. The reaction temperature is relatively high, while the imatinib base is sensitive to heat, and is susceptible to thermal degradation, which leads to a low product yield of only 85%˜90%.
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