Gleevec Synthesis Research

Gleevec (imatinib mesylate) was an inhibitor of tyrosine kinases for treating chronic myeloid leukemia(CML) and gastrointestinal stromal tumors(GIST), which was empol-dered by Novartis. It was a new therapy of cancer.Gleevec([4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridyl)-2-pyri-midinyl]amino]phenyl]benzamide methanesulfonate) was the first target drug to be rationally designed based on a molecular abnormality in CML, so research on the synthesis of Gleevec played an important role.In this dissertation, comparing several ways, the synthesis of Gleevec was accomplished from DMF, 3-acetylpyridine, 2-amino-4-nitrotoluene and 4-bromomethyl-benzonitrile. Further improved methods were investigated for the synthesis of several important intermediates.The synthetic route was characterized by available raw materials, higher yield and more moderate conditions. The intermediates(excpet DMFDMA) were solid, easy to be purified and handled. Thus, the route was suitable for industrial production. The structure of the synthetic products were characterized by Infrared Spectroscopy(IR), Mass Spectra (MS) and ~1H Nuclear Magnetic Resonance(NMR). The results proved: the structures of the products conformed to the designed requirement. This can prognosticate the synthetic route was available, practical and effective.