Synthesis Of Imatinib Mesylate

Protein tyrosine kinases play a key role in signal transduction pathways regulating essential cellular processes such as growth,differentiation,and death.A role in the etiology of different human diseases including proliferative,inflammatory responses,and tumors has been ascribed to protein of this family pathologically endowed with a deregulates constitutiveactivity.At present,many inhibitors have been found,such as gefitinib,erlotinib,sorafenib and imatinib.Imatinib mesylate is known as a selective inhibitor of Bcr-Abl tyrosine kinase for treating chronic myeloid leukemia(CML),Philadelphia chromosome positive leukemia,and patients in chronic phase and in blast crisis,accelerated phase and also for malignant gastrointestinal stromal tumors(GIST),which was developed by Novartis and approvaled by the U.S.Food and Drug Administration(FDA)in May 2001.The durg specially inhibits the activity of Bcr-Abl tyrosine kinase with efficiency and low toxicity.The chemical name of imatinib mesylate is 4-(4-methyl-piperazin-1-ylmethyl)-N-[4-methyl-3-[(4-pyridin-3-yl)pyrimidin-2-ylamino]-phenyl]-benzamide mesylate.Because of efficiency and low toxicity,imatinib becomes one of the most promising anticancer drugs.So research on the synthesis of imatinib plays an important role.The synthetic route was charaterized by available raw materials,higher yield and more moderate.Imatinib Mesylate was prepared by addition,cyclization,reduction,acylation with the 2-methyl-5-nitroaniline as the starting material.The process of addition,cyclization,reduction,acylation was improved.The total yield was achieved more than 40% and the purity of the final product was achieved 99.81% by HPLC.